Liberman M Charles
Department of Otolaryngology, Harvard Medical School, Eaton Peabody Laboratories, Massachusetts Eye and Ear, 243 Charles St., Boston, MA, 02114, USA.
F1000Res. 2017 Jun 16;6:927. doi: 10.12688/f1000research.11310.1. eCollection 2017.
The classic view of sensorineural hearing loss has been that the primary damage targets are hair cells and that auditory nerve loss is typically secondary to hair cell degeneration. Recent work has challenged that view. In noise-induced hearing loss, exposures causing only reversible threshold shifts (and no hair cell loss) nevertheless cause permanent loss of >50% of the synaptic connections between hair cells and the auditory nerve. Similarly, in age-related hearing loss, degeneration of cochlear synapses precedes both hair cell loss and threshold elevation. This primary neural degeneration has remained a "hidden hearing loss" for two reasons: 1) the neuronal cell bodies survive for years despite loss of synaptic connection with hair cells, and 2) the degeneration is selective for auditory nerve fibers with high thresholds. Although not required for threshold detection when quiet, these high-threshold fibers are critical for hearing in noisy environments. Research suggests that primary neural degeneration is an important contributor to the perceptual handicap in sensorineural hearing loss, and it may be key to the generation of tinnitus and other associated perceptual anomalies. In cases where the hair cells survive, neurotrophin therapies can elicit neurite outgrowth from surviving auditory neurons and re-establishment of their peripheral synapses; thus, treatments may be on the horizon.
感音神经性听力损失的传统观点认为，主要的损伤靶点是毛细胞，而听神经损失通常继发于毛细胞变性。最近的研究对这一观点提出了挑战。在噪声性听力损失中，仅导致可逆性阈移（且无毛细胞损失）的暴露仍会导致毛细胞与听神经之间超过50%的突触连接永久性丧失。同样，在年龄相关性听力损失中，耳蜗突触的退化先于毛细胞损失和阈值升高。这种原发性神经退化一直是一种“隐性听力损失”，原因有两个：1）尽管与毛细胞的突触连接丧失，但神经元细胞体仍能存活数年；2）退化对高阈值的听神经纤维具有选择性。虽然在安静时阈值检测不需要这些高阈值纤维，但它们对于嘈杂环境中的听力至关重要。研究表明，原发性神经退化是感音神经性听力损失中感知障碍的一个重要因素，它可能是耳鸣和其他相关感知异常产生的关键。在毛细胞存活的情况下，神经营养素疗法可以促使存活的听觉神经元长出神经突并重新建立其外周突触；因此，治疗方法可能即将出现。
