Department of Otology and Skull Base Surgery, Hearing Research Key Lab of Health Ministry of China, Eye & Ear Nose and Throat Hospital, Fudan University, Shanghai, China.
Electron Microscopy Facility, Institute of Neuroscience, Shanghai Institutes for Biological Science, Chinese Academy of Sciences, Shanghai, China.
J Histochem Cytochem. 2018 Nov;66(11):801-812. doi: 10.1369/0022155418773746. Epub 2018 May 15.
Intratympanic gentamicin (ITG) has been used to treat refractory Ménière's disease. Disequilibrium after ITG was still a challenge for some patients, and the underlying mechanism is poorly understood. Our previous study demonstrated that gentamicin distributed in the bilateral vestibular efferent neurons (VEN) after ITG; however, does it lead to VEN damage and cause further disequilibrium in patients following ITG? In this study, we observed severe damaged gentamicin-positive neurons of VEN and severe fractured myelin layer plates around neural fibers when viewed under transmission electron microscopy at day 3 after ITG. At day 30, neurons of VEN presented with relatively normal structures. Compared with the control group, the total number of choline acetyltransferase (CHAT) immunolabeling neurons in bilateral VEN showed a significant decrease both at day 3 and day 30. However, there was no significant difference in the total number of CHAT immunolabeling neurons between day 3 and day 30. It indicates that gentamicin is not only retrogradely transported into bilateral VEN, but also results in the degeneration of VEN after ITG. These findings may be related to patients' disequilibrium symptom after ITG. Furthermore, we speculate that VEN may play a role in vestibular compensation.
鼓室内庆大霉素（ITG）已被用于治疗难治性梅尼埃病。但对于一些患者来说，接受 ITG 治疗后仍会出现平衡障碍，其潜在机制尚不清楚。我们之前的研究表明，庆大霉素在接受 ITG 治疗后分布在双侧前庭传出神经元（VEN）中；然而，它是否会导致 VEN 损伤，并导致接受 ITG 治疗的患者进一步出现平衡障碍？在这项研究中，我们在接受 ITG 治疗后第 3 天通过透射电子显微镜观察到 VEN 中严重受损的庆大霉素阳性神经元和神经纤维周围严重断裂的髓鞘板层。在第 30 天，VEN 的神经元呈现出相对正常的结构。与对照组相比，双侧 VEN 中胆碱乙酰转移酶（CHAT）免疫标记神经元的总数在第 3 天和第 30 天都显著减少。然而，第 3 天和第 30 天之间 CHAT 免疫标记神经元的总数没有显著差异。这表明庆大霉素不仅逆行运输到双侧 VEN，而且在接受 ITG 治疗后还导致 VEN 退化。这些发现可能与患者接受 ITG 治疗后的平衡障碍症状有关。此外，我们推测 VEN 可能在前庭代偿中起作用。
