Cochlear NMDA Receptors as a Therapeutic Target of Noise-Induced Tinnitus
Cochlear NMDA Receptors as a Therapeutic Target of Noise-Induced Tinnitus
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DOI：
10.1159/000374000
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发表时间：
2015-01-01
影响因子：
--
通讯作者：
Singer, Wibke
中科院分区：
文献类型：
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作者：
Bing, Dan;Lee, Sze Chim;Singer, Wibke
背景：越来越多的证据表明，尽管听觉敏感度正常，耳鸣仍可发生，可能与耳蜗神经部分变性和内毛细胞突触受损有关。即使在适度的噪声暴露后，也可能会对IHC突触和去传入造成损害。对于水杨酸和噪声诱导的耳鸣，N-甲基-d-天冬氨酸(NMDA)受体的异常激活和相关的听神经兴奋被认为是耳蜗性耳鸣的起源。因此，NMDA受体抑制被认为是治疗突触病理性耳鸣的一种药理学方法。方法：在急性创伤性噪声耳鸣动物模型上，应用NMDA受体拮抗剂AM-101(盐酸埃斯氯胺凝胶，Auris Medical AG，瑞士巴塞尔)进行圆窗应用试验。这项研究包括量化IHC带状突触作为去传入的相关性，以及测量听觉脑干反应(ABR)作为声音诱导的听神经活动的指示。结果：AM-101可减轻外伤性耳蜗听神经IHC条带的丢失，并能对抗ABR波I波幅的下降。结论：局部圆窗应用AM-101可能是治疗突触性耳鸣的一种有前途的治疗手段。版权所有(C)2015年S.Karger AG，巴塞尔
Background: Accumulating evidence suggests that tinnitus may occur despite normal auditory sensitivity, probably linked to partial degeneration of the cochlear nerve and damage of the inner hair cell (IHC) synapse. Damage to the IHC synapses and deafferentation may occur even after moderate noise exposure. For both salicylate-and noise-induced tinnitus, aberrant N-methyl-d-aspartate (NMDA) receptor activation and related auditory nerve excitation have been suggested as origin of cochlear tinnitus. Accordingly, NMDA receptor inhibition has been proposed as a pharmacologic approach for treatment of synaptopathic tinnitus. Methods: Round-window application of the NMDA receptor antagonist AM-101 (Esketamine hydrochloride gel; Auris Medical AG, Basel, Switzerland) was tested in an animal model of tinnitus induced by acute traumatic noise. The study included the quantification of IHC ribbon synapses as a correlate for deafferentation as well as the measurement of the auditory brainstem response (ABR) to close-threshold sensation level stimuli as an indication of sound-induced auditory nerve activity. Results: We have shown that AM-101 reduced the trauma-induced loss of IHC ribbons and counteracted the decline of ABR wave I amplitude generated in the cochlea/auditory nerve. Conclusion: Local round-window application of AM-101 may be a promising therapeutic intervention for the treatment of synaptopathic tinnitus. Copyright (C) 2015 S. Karger AG, Basel