Bilirubin induces auditory neuropathy in neonatal guinea pigs via auditory nerve fiber damage
Bilirubin induces auditory neuropathy in neonatal guinea pigs via auditory nerve fiber damage
复制标题
胆红素通过听觉神经纤维损伤诱发新生豚鼠听觉神经病变
DOI：
10.1002/jnr.23107
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发表时间：
2012-11-01
影响因子：
4.2
通讯作者：
Yin, Shan-Kai
中科院分区：
文献类型：
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作者：
Ye, Hai-Bo;Shi, Hai-Bo;Yin, Shan-Kai
胆红素可导致新生儿高胆红素血症的暂时性或永久性感觉神经性耳聋。然而，胆红素引起的外周听觉系统损伤的潜在靶点和生理效应尚不清楚。通过对新生豚鼠耳蜗肌功能测定和内耳电子显微镜成像，发现胆红素暴露可引起豚鼠复合动作电位(CAP)和听性脑干反应(ABR)阈值升高，给药后1小时明显升高，8小时达高峰。ABR和CAP的阈值升高与波潜伏期延迟和波间间期延长有关。注射后72小时，除CAP波幅外，其余指标均恢复到对照水平。耳蜗微音学在实验过程中保持不变。形态异常与电生理障碍相一致，治疗8h后，基底角听神经纤维(ANF)减少，螺旋神经节神经元(SGN)和ANF的髓鞘损伤，内毛细胞(IHC)下的I型传入终末消失，但毛细胞没有丢失。与电生理结果相似，治疗10d后，除心钠素减少外，形态改变大多逆转。这些结果表明，新生豚鼠高胆红素血症损害了以IHC突触和SGN的髓鞘及其纤维为主要靶点的听觉外周神经机制。我们的观察表明高胆红素血症和听神经病之间存在潜在的联系。(C)2012年威利期刊公司。
Bilirubin can cause temporary or permanent sensorineural deafness in newborn babies with hyperbilirubinemia. However, the underlying targets and physiological effects of bilirubin-induced damage in the peripheral auditory system are unclear. Using cochlear functional assays and electron microscopy imaging of the inner ear in neonatal guinea pigs, we show here that bilirubin exposure resulted in threshold elevation in both compound action potential (CAP) and auditory brainstem response (ABR), which was apparent at 1 hr and peaked 8 hr after drug administration. The threshold elevation was associated with delayed wave latencies and elongated interwave intervals in ABR and CAP. At 72 hr postinjection, these measures returned to control levels, except for the CAP amplitude. Cochlear microphonics remained unchanged during the experiment. Morphological abnormalities were consistent with the electrophysiological dysfunction, revealing fewer auditory nerve fibers (ANFs) in the basal turn, myelin sheath lesions of spiral ganglion neurons (SGNs) and ANFs, and loss of type 1 afferent endings beneath inner hair cells (IHCs) without loss of hair cells at 8 hr posttreatment. Similar to the electrophysiological findings, morphological changes were mostly reversed 10 days after treatment, except for the ANF reduction in the basal turn. These results suggest that hyperbilirubinemia in neonatal guinea pigs impaired auditory peripheral neuromechanisms that targeted mainly the IHC synapses and the myelin sheath of SGNs and their fibers. Our observations indicate a potential connection between hyperbilirubinemia and auditory neuropathy. (c) 2012 Wiley Periodicals, Inc.