Department of Otolaryngology-Head and Neck Surgery, Nihon University School of Medicine, Tokyo, Japan.
Department of Functional Morphology, Division of Cell Regeneration and Transplantation, Nihon University School of Medicine, Tokyo, Japan.
PLoS One. 2020 Aug 27;15(8):e0237231. doi: 10.1371/journal.pone.0237231. eCollection 2020.
In this study, we examined the effect of differing gap lengths on regeneration of transected recurrent laryngeal nerves using silicon tubes containing type I collagen gel and the ability of this regeneration to result in restoration of vocal fold movements in rats. We simulated nerve gaps in Sprague-Dawley rats by transecting the left recurrent laryngeal nerves and bridged the nerve stumps using silicon tubes containing type 1 collagen gel. Three experimental groups, in which the gap lengths between the stumps were 1, 3, or 5 mm, were compared with a control group in which the nerve was transected but was not bridged. After surgery, we observed vocal fold movements over time with a laryngoscope. At week 15, we assessed the extent of nerve regeneration in the tube, histologically and electrophysiologically. We also assessed the degree of atrophy of the thyroarytenoid muscle (T/U ratio). Restoration of vocal fold movements was observed in 9 rats in the 1-mm group, in 6 rats in the 3-mm group, and in 3 rats in the 5-mm group. However, in most rats, restoration was temporary, with only one rat demonstrating continued vocal fold movements at week 15. In electromyograph, evoked potentials were observed in rats in the 1-mm and 3-mm groups. Regenerated tissue in the tube was thickest in the 1-mm group, followed by the 3-mm and 5-mm groups. The regenerated tissue showed the presence of myelinated and unmyelinated nerve fibers. In assessment of thyroarytenoid muscle atrophy, the T/U ratio was highest in the 1-mm group, followed by the 3-mm and 5-mm groups. We successfully regenerated the nerves and produced a rat model of recurrent laryngeal nerve regeneration that demonstrated temporary recovery of vocal fold movements. This rat model could be useful for assessing novel treatments developing in the future.
在这项研究中，我们研究了使用含有 I 型胶原凝胶的硅管来桥接神经残端，不同的神经间隙长度对切断的喉返神经再生的影响，以及这种再生能否使大鼠的声带运动恢复。我们通过切断左侧喉返神经模拟神经间隙，使用含有 I 型胶原凝胶的硅管桥接神经残端。我们将实验组（神经间隙长度分别为 1、3 或 5mm）与对照组（神经切断但未桥接）进行比较。手术后，我们通过喉镜观察声带运动随时间的变化。在第 15 周，我们从组织学和电生理学方面评估了管内神经再生的程度，还评估了甲状腺动肌（T/U 比）萎缩的程度。在 1mm 组的 9 只大鼠、3mm 组的 6 只大鼠和 5mm 组的 3 只大鼠中观察到声带运动的恢复。然而，在大多数大鼠中，恢复是暂时的，只有 1 只大鼠在第 15 周时仍持续有声带运动。在肌电图中，1mm 组和 3mm 组的大鼠可观察到诱发电位。管内再生组织在 1mm 组最厚，其次是 3mm 组和 5mm 组。再生组织显示有髓和无髓神经纤维的存在。在评估甲状腺动肌萎缩时，T/U 比在 1mm 组最高，其次是 3mm 组和 5mm 组。我们成功地再生了神经，并建立了一个大鼠喉返神经再生模型，该模型可暂时恢复声带运动。这种大鼠模型可能有助于评估未来开发的新疗法。
