Center for Hearing & Deafness, SUNY at Buffalo, 137 Cary Hall, Buffalo, NY 14214, USA.
Hear Res. 2013 Jan;295:100-13. doi: 10.1016/j.heares.2012.11.016. Epub 2012 Nov 27.
High doses of sodium salicylate (SS) have long been known to induce temporary hearing loss and tinnitus, effects attributed to cochlear dysfunction. However, our recent publications reviewed here show that SS can induce profound, permanent, and unexpected changes in the cochlea and central nervous system. Prolonged treatment with SS permanently decreased the cochlear compound action potential (CAP) amplitude in vivo. In vitro, high dose SS resulted in a permanent loss of spiral ganglion neurons and nerve fibers, but did not damage hair cells. Acute treatment with high-dose SS produced a frequency-dependent decrease in the amplitude of distortion product otoacoustic emissions and CAP. Losses were greatest at low and high frequencies, but least at the mid-frequencies (10-20 kHz), the mid-frequency band that corresponds to the tinnitus pitch measured behaviorally. In the auditory cortex, medial geniculate body and amygdala, high-dose SS enhanced sound-evoked neural responses at high stimulus levels, but it suppressed activity at low intensities and elevated response threshold. When SS was applied directly to the auditory cortex or amygdala, it only enhanced sound evoked activity, but did not elevate response threshold. Current source density analysis revealed enhanced current flow into the supragranular layer of auditory cortex following systemic SS treatment. Systemic SS treatment also altered tuning in auditory cortex and amygdala; low frequency and high frequency multiunit clusters up-shifted or down-shifted their characteristic frequency into the 10-20 kHz range thereby altering auditory cortex tonotopy and enhancing neural activity at mid-frequencies corresponding to the tinnitus pitch. These results suggest that SS-induced hyperactivity in auditory cortex originates in the central nervous system, that the amygdala potentiates these effects and that the SS-induced tonotopic shifts in auditory cortex, the putative neural correlate of tinnitus, arises from the interaction between the frequency-dependent losses in the cochlea and hyperactivity in the central nervous system.
高剂量的水杨酸钠（SS）长期以来一直被认为会导致暂时的听力损失和耳鸣，这些影响归因于耳蜗功能障碍。然而，我们在这里回顾的最近的出版物表明，SS 可以引起耳蜗和中枢神经系统的深刻、持久和意外的变化。长期用 SS 治疗会使体内的耳蜗复合动作电位（CAP）幅度永久降低。在体外，高剂量的 SS 导致螺旋神经节神经元和神经纤维的永久性丧失，但不会损伤毛细胞。急性高剂量 SS 处理会导致畸变产物耳声发射和 CAP 幅度随频率依赖性降低。损失在低频和高频最大，但在中频（10-20 kHz）最小，中频对应于行为测量的耳鸣音高。在听觉皮层、内侧膝状体和杏仁核中，高剂量的 SS 在高刺激水平下增强了声音诱发的神经反应，但在低强度下抑制了活动并提高了反应阈值。当 SS 直接施加到听觉皮层或杏仁核时，它只会增强声音诱发的活动，而不会提高反应阈值。电流源密度分析显示，全身性 SS 处理后，听觉皮层的超颗粒层中的电流流增强。全身性 SS 处理还改变了听觉皮层和杏仁核的调谐；低频和高频多单位簇将其特征频率向上或向下移到 10-20 kHz 范围内，从而改变了听觉皮层的音调图，并增强了与耳鸣音高相对应的中频的神经活动。这些结果表明，SS 诱导的听觉皮层过度活跃源于中枢神经系统，杏仁核增强了这些效应，而听觉皮层的音调图移位，即耳鸣的潜在神经相关，源于耳蜗中频率依赖性损失与中枢神经系统过度活跃之间的相互作用。
