El-Badry Mohamed M, Ding Da-lian, McFadden Sandra L, Eddins Ann C
Otolaryngology Department, Audiology Unit, El-Minia University Hospitals, El-Minia University, El-Minia, Egypt.
Eur J Neurosci. 2007 Mar;25(5):1437-46. doi: 10.1111/j.1460-9568.2007.05401.x.
The goals were to study the physiological effects of auditory nerve myelinopathy in chinchillas and to test the hypothesis that myelin abnormalities could account for auditory neuropathy, a hearing disorder characterized by absent auditory brainstem responses (ABRs) with preserved outer hair cell function. Doxorubicin, a cytotoxic drug used as an experimental demyelinating agent, was injected into the auditory nerve bundle of 18 chinchillas; six other chinchillas were injected with vehicle alone. Cochlear microphonics, compound action potentials (CAPs), inferior colliculus evoked potentials (IC-EVPs), cubic distortion product otoacoustic emissions and ABRs were recorded before and up to 2 months after injection. Cochleograms showed no hair cell loss in any of the animals and measures of outer hair cell function were normal (cubic distortion product otoacoustic emissions) or enhanced (cochlear microphonics) after injection. ABR was present in animals with mild myelin damage (n = 10) and absent in animals with severe myelin damage that included the myelin surrounding spiral ganglion cell bodies and fibers in Rosenthal's canal (n = 8). Animals with mild damage had reduced response amplitudes at 1 day, followed by recovery of CAP and enhancement of the IC-EVP. In animals with severe damage, CAP and IC-EVP thresholds were elevated, amplitudes were reduced, and latencies were prolonged at 1 day and thereafter. CAPs deteriorated over time, whereas IC-EVPs partially recovered; latencies remained consistently prolonged despite changes in amplitudes. The results support auditory nerve myelinopathy as a possible pathomechanism of auditory neuropathy but indicate that myelinopathy must be severe before physiological measures are affected.
本研究旨在探讨毛丝鼠听觉神经髓鞘病的生理效应，并验证以下假设：髓鞘异常可能是听觉神经病的病因，听觉神经病是一种听力障碍，其特征为听觉脑干反应（ABR）消失而外毛细胞功能保留。将阿霉素（一种用作实验性脱髓鞘剂的细胞毒性药物）注射到18只毛丝鼠的听神经束中；另外6只毛丝鼠仅注射赋形剂。在注射前及注射后长达2个月内记录耳蜗微音器电位、复合动作电位（CAP）、下丘诱发电位（IC-EVP）、立方畸变产物耳声发射和ABR。耳蜗电图显示所有动物均无毛细胞丢失，且注射后外毛细胞功能指标正常（立方畸变产物耳声发射）或增强（耳蜗微音器电位）。轻度髓鞘损伤的动物（n = 10）存在ABR，而重度髓鞘损伤的动物（包括围绕螺旋神经节细胞体和罗森塔尔管内纤维的髓鞘）（n = 8）则无ABR。轻度损伤的动物在1天时反应幅度降低，随后CAP恢复，IC-EVP增强。在重度损伤的动物中，CAP和IC-EVP阈值升高，幅度降低，潜伏期在1天及之后延长。CAP随时间推移而恶化，而IC-EVP部分恢复；尽管幅度有所变化，但潜伏期始终延长。这些结果支持听觉神经髓鞘病可能是听觉神经病的发病机制，但表明在生理指标受到影响之前，髓鞘病必须严重。
