Electrophysiological correlates of progressive sensorineural pathology in carboplatin-treated chinchillas

Electrophysiological correlates of progressive sensorineural pathology in carboplatin-treated chinchillas
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DOI:
10.1016/j.brainres.2006.11.078
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发表时间:
2007-02-23
期刊:
影响因子:
2.9
通讯作者:
McFadden, Sandra L.
McFadden, Sandra L.
中科院分区:
医学3区
文献类型:
--
作者:
El-Badry, Mohamed M.;McFadden, Sandra L.

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卡铂会对栗鼠耳蜗内的听神经纤维、螺旋神经节神经元(SGN)和内毛细胞(IHC)造成进行性损害,但不会损害外毛细胞。注射后1h内,IHC下的许多传入终末和围绕SGN突起的髓鞘板层出现空泡化。注射后一天,大约一半的神经纤维丢失。IHC在2天内完好无损,但3天后20-30%丢失。采用耳蜗微音学(CM)、畸变产物耳声发射(DPOAE)、总和电位(SP)、复合动作电位(CAP)和中脑诱发电位(IC-EVP)等电生理方法,对4只龙猫在注射卡铂(75 mg/kg ip)前和注射后1h、12h、1d、3d、5d、7d和14d的电生理变化进行了研究。CM和DPOAEs趋于不变或增强。CAP和SP变化不大,直到第3天,所有动物的波幅均降低,CAP阈值升高9分贝;在第3天和第5天,波幅进一步下降,但此后不再下降。IC-EVP波幅在第3天或第5天下降,但阈值相对不变。所有动物的IC-EVP在第7天到第14天都有一定程度的恢复,其中一只在第14天有70%的增强。结果表明,阈值和波幅测量直到超过一些相对较高的损伤阈值水平时才能发现外周病变。这对于监测动物和人类的外周损伤和解释电生理测试结果具有重要意义。(C)爱思唯尔2006年。版权所有。
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. (c) 2006 Elsevier BY. All rights reserved.