Müller Marcus, Klinke Rainer, Arnold Wolfgang, Oestreicher Elmar
Department of Physiology II, University Frankfurt, Theodor-Stern-Kai 7, D-60590, Frankfurt am Main, Germany.
Hear Res. 2003 Sep;183(1-2):37-43. doi: 10.1016/s0378-5955(03)00217-x.
Ototoxicity of salicylate is accompanied by a temporary hearing loss and tinnitus and has therefore been used to study tinnitus in animal models. Salicylate induced elevated central auditory activity has been interpreted as a correlate of tinnitus. Whether this elevated activity in the central auditory system is due to an increased activity in the auditory nerve is still under discussion. To explore this issue, we recorded the activity of single auditory nerve fibres in anaesthetised gerbils following systemic injection of salicylic acid. Firstly, compound action potential (CAP) thresholds were determined at 5-0 min intervals. Fifteen to 30 min after 200 mg/kg salicylic acid, threshold loss developed in the high frequency range. At 2 h CAP threshold loss reached a plateau amounting to 15-20 dB above 16 kHz, 0-5 dB below 2 kHz. An almost immediate start of threshold loss was observed after 400 mg/kg salicylic acid. A plateau of threshold loss was reached after 1.5 h with values of 25 dB in the high, 5-10 dB in the low frequency range. Secondly, responses of single auditory nerve fibres were studied after administration of 200 mg/kg salicylic acid. Frequency tuning curves and rate intensity (RI) functions at characteristic frequency (CF) were measured. Two hours and more after application, single fibre thresholds were elevated by about 20 dB at all CFs. Sharpness of tuning was reduced. Mean spontaneous rate was significantly reduced at CFs below 5 kHz (mean: 44 vs 28 AP/s). At CFs above 5 kHz mean spontaneous rate remained unchanged. In RI functions no change in maximum discharge rate was observed. The altered response properties can be interpreted by the known effects of salicylate on the prestin mediated active process of the outer hair cells. The elevated activity in the central auditory system after salicylate intoxication thus cannot be caused by cochlear nerve hyperactivity.
水杨酸盐的耳毒性伴有暂时性听力损失和耳鸣，因此被用于动物模型中耳鸣的研究。水杨酸盐诱导的中枢听觉活动增强被认为是耳鸣的一个相关因素。中枢听觉系统中这种增强的活动是否是由于听神经活动增加仍在讨论中。为了探讨这个问题，我们在全身注射水杨酸后，记录了麻醉沙土鼠单根听神经纤维的活动。首先，每隔5 - 0分钟测定复合动作电位（CAP）阈值。注射200mg/kg水杨酸后15至30分钟，高频范围内出现阈值损失。2小时时，CAP阈值损失达到平台期，在16kHz以上达到15 - 20dB，在2kHz以下为0 - 5dB。注射400mg/kg水杨酸后，几乎立即开始出现阈值损失。1.5小时后达到阈值损失平台期，高频值为25dB，低频范围为5 - 10dB。其次，在给予200mg/kg水杨酸后研究单根听神经纤维的反应。测量了特征频率（CF）处的频率调谐曲线和速率强度（RI）函数。给药2小时及更长时间后，所有CF处的单纤维阈值升高约20dB。调谐锐度降低。在低于5kHz的CF处，平均自发率显著降低（平均值：44对28次动作电位/秒）。在高于5kHz的CF处，平均自发率保持不变。在RI函数中，未观察到最大放电率的变化。水杨酸盐对外毛细胞中prestin介导的主动过程的已知作用可以解释反应特性的改变。因此，水杨酸盐中毒后中枢听觉系统中增强的活动不可能是由耳蜗神经活动亢进引起的。
