Use of non-invasive measures to predict cochlear synapse counts
Use of non-invasive measures to predict cochlear synapse counts
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DOI：
10.1016/j.heares.2018.10.006
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发表时间：
2018-12-01
期刊：
影响因子：
2.8
通讯作者：
Konrad-Martin, Dawn
中科院分区：
文献类型：
--
作者：
Bramhall, Naomi F.;McMillan, Garnett P.;Konrad-Martin, Dawn
耳蜗突触病，即内毛细胞 (IHC) 和听觉神经纤维之间突触连接的丧失，已在衰老、噪音和耳毒性药物暴露（人类获得性感音神经性听力损失的三个常见原因）的动物模型中得到记录。在这些模型中，突触病在阈值敏感性变化或毛细胞损失之前就开始了。因此，这种潜在的损伤可能隐藏在正常阈值听力图后面。由于无法在活体人类中直接确认耳蜗突触丧失，因此需要进行非侵入性检测来诊断。在听觉阈值正常的动物中，听觉脑干反应 (ABR) 第一波的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，使单独使用 ABR 作为诊断措施变得复杂。这项研究使用按年龄分级的一系列小鼠和偏最小二乘回归方法来模拟结构-功能关系，表明少量 ABR 和畸变产物耳声发射 (DPOAE) 测量的结合可以预测不同耳蜗频率下的突触带计数，每个 IHC 的突触带计数与其真实值相差不超过 1-2 个。相比之下，使用按年龄分级的一系列小鼠进行训练的模型过度预测了一小部分暴露于噪声的年轻小鼠样本中的突触计数，这可能是由于衰老小鼠和暴露于噪声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 识别人类突触/神经元损失的非侵入性方法提供了部分验证。由 Elsevier B.V. 出版
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. Published by Elsevier B.V.