VA RR&D National Center for Rehabilitative Auditory Research (NCRAR), VA Portland Health Care System, Portland, OR, 97239, USA; Department of Otolaryngology/Head & Neck Surgery, Oregon Health & Science University, Portland, OR, 97239, USA.
VA RR&D National Center for Rehabilitative Auditory Research (NCRAR), VA Portland Health Care System, Portland, OR, 97239, USA; Department of Otolaryngology/Head & Neck Surgery, Oregon Health & Science University, Portland, OR, 97239, USA.
Hear Res. 2018 Dec;370:113-119. doi: 10.1016/j.heares.2018.10.006. Epub 2018 Oct 13.
Cochlear synaptopathy, the loss of synaptic connections between inner hair cells (IHCs) and auditory nerve fibers, has been documented in animal models of aging, noise, and ototoxic drug exposure, three common causes of acquired sensorineural hearing loss in humans. In each of these models, synaptopathy begins prior to changes in threshold sensitivity or loss of hair cells; thus, this underlying injury can be hidden behind a normal threshold audiogram. Since cochlear synaptic loss cannot be directly confirmed in living humans, non-invasive assays will be required for diagnosis. In animals with normal auditory thresholds, the amplitude of wave 1 of the auditory brainstem response (ABR) is highly correlated with synapse counts. However, synaptopathy can also co-occur with threshold elevation, complicating the use of the ABR alone as a diagnostic measure. Using an age-graded series of mice and a partial least squares regression approach to model structure-function relationships, this study shows that the combination of a small number of ABR and distortion product otoacoustic emission (DPOAE) measurements can predict synaptic ribbon counts at various cochlear frequencies to within 1-2 synapses per IHC of their true value. In contrast, the model, trained using the age-graded series of mice, overpredicted synapse counts in a small sample of young noise-exposed mice, perhaps due to differences in the underlying pattern of damage between aging and noise-exposed mice. These results provide partial validation of a noninvasive approach to identify synaptic/neuronal loss in humans using ABRs and DPOAEs.
耳蜗突触病，即内毛细胞 (IHC) 和听神经纤维之间突触连接的丧失，已在衰老、噪声和耳毒性药物暴露的动物模型中得到证实，这三种情况是人类获得性感觉神经性听力损失的常见原因。在这些模型中的每一种中，突触病都发生在阈值敏感性变化或毛细胞丧失之前；因此，这种潜在的损伤可能隐藏在正常阈值听力图的背后。由于不能直接在活体人类中证实耳蜗突触丢失，因此需要非侵入性检测来进行诊断。在听觉阈值正常的动物中，听觉脑干反应 (ABR) 的波 1 幅度与突触计数高度相关。然而，突触病也可能与阈值升高同时发生，这使得 ABR 单独作为诊断措施的使用变得复杂。本研究使用一系列年龄分级的小鼠和偏最小二乘回归方法来模拟结构-功能关系，结果表明，少量 ABR 和畸变产物耳声发射 (DPOAE) 测量的组合可以预测各种耳蜗频率的突触带计数，其与真实值相差 1-2 个突触。相比之下，该模型在一小部分年轻噪声暴露的小鼠中过度预测了突触计数，这可能是由于衰老和噪声暴露的小鼠之间潜在的损伤模式存在差异。这些结果为使用 ABR 和 DPOAE 来识别人类的突触/神经元损失的非侵入性方法提供了部分验证。
