Recently, a pathological condition called cochlear synaptopathy has been clarified, and as a disorder of the auditory nerve synapses that occurs prior to failure of hair cells, it has been recognized as a major cause of sensorineural hearing loss. However, cochlear synaptopathy is untreatable. Inhibition of rho-associated coiled-coil containing protein kinase (ROCK), a serine-threonine protein kinase, has been reported to have neuroprotective and regenerative effects on synaptic pathways in the nervous system, including those in the inner ear. We previously demonstrated the regenerative effect of the ROCK inhibitor, Y-27632, on an excitotoxic cochlear nerve damage model in vitro. In this study, we aimed to validate the effect of ROCK inhibition on mice with cochlear synaptopathy induced by laser-induced shock wave (LISW) in vivo. After the elevation of ROCK1/2 expression in the damaged cochlea was confirmed, we administered Y-27632 locally via the middle ear. The amplitude of wave I in the auditory brainstem response and the number of synapses in the Y-27632-treated cochlea increased significantly. These results clearly demonstrate that ROCK inhibition has a promising clinical application in the treatment of cochlear synaptopathy, which is the major pathology of sensorineural hearing loss.

中文翻译：

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Y-27632，一种 ROCK 抑制剂，可改善激光诱导冲击波 (LISW) 诱导的小鼠耳蜗突触病

最近，一种被称为耳蜗突触病的病理状况得到了阐明，作为一种在毛细胞衰竭之前发生的听神经突触障碍，它被认为是感音神经性听力损失的主要原因。然而，耳蜗突触病是无法治愈的。据报道，抑制含有 rho 相关卷曲螺旋的蛋白激酶 (ROCK)，一种丝氨酸-苏氨酸蛋白激酶，对神经系统中的突触通路具有神经保护和再生作用，包括内耳中的突触通路。我们之前证明了 ROCK 抑制剂 Y-27632 对体外兴奋性耳蜗神经损伤模型的再生作用。在本研究中，我们旨在验证 ROCK 抑制对体内激光诱导冲击波 (LISW) 诱导的耳蜗突触病小鼠的影响。在确认受损耳蜗中 ROCK1/2 表达升高后，我们通过中耳局部施用 Y-27632。听觉脑干反应中波 I 的幅度和 Y-27632 处理的耳蜗中的突触数量显着增加。这些结果清楚地表明，ROCK 抑制在治疗耳蜗突触病方面具有广阔的临床应用前景，而耳蜗突触病是感音神经性听力损失的主要病理。