Mori Yuko, Shiotani Akihiro, Saito Koichiro, Araki Koji, Ikeda Ken, Nakagawa Masaya, Watabe Kazuhiko, Ogawa Kaoru
Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
Laryngoscope. 2007 Jul;117(7):1313-8. doi: 10.1097/MLG.0b013e31805f681f.
OBJECTIVES/HYPOTHESIS: We have previously shown that gene therapy using Insulin-like growth factor (IGF)-I, glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF), or a combination of these trophic factors, is a treatment option for recurrent laryngeal nerve (RLN) palsy. However, there remain some difficulties preventing this option from becoming a common clinical therapy for RLN injury. Thus, we need to develop novel treatment option that overcomes the problems of gene therapy.R(-)-1-(benzothiophen-5-yl)-2-[2-N,N-diethylamino]ethoxy]ethanol hydrochloride (T-588), a synthetic compound, is known to have neuroprotective effects on neural cells. In the present study, the possibility of new drug treatments using T-588 for RLN injury was assessed using rat models.
Animal study.
Animals were administered T-588 for 4 weeks. The neuroprotective effects of T-588 administration after vagal nerve avulsion and neurofunctional recovery after recurrent laryngeal nerve crush were studied using motoneuron cell counting, evaluation of choline acetyltransferase immunoreactivity, the electrophysiologic examination, and the re-mobilization of the vocal fold.
T-588 administration successfully prevented motoneuron loss and ameliorated the choline acetyltransferase immunoreactivity in the ipsilateral nucleus ambiguus after vagal nerve avulsion. Significant improvements of motor nerve conduction velocity of the RLN and vocal fold movement were observed in the treatment group when compared to controls.
These results indicate that oral administration of T-588 might be a promising therapeutic option in treating peripheral nerve injury.
目的/假设:我们之前已经表明,使用胰岛素样生长因子(IGF)-I、胶质细胞源性神经营养因子(GDNF)和脑源性神经营养因子(BDNF),或这些营养因子的组合进行基因治疗,是喉返神经(RLN)麻痹的一种治疗选择。然而,仍然存在一些困难,阻碍了这种选择成为RLN损伤的常见临床治疗方法。因此,我们需要开发一种新的治疗方法来克服基因治疗的问题。R(-)-1-(苯并噻吩-5-基)-2-[2-N,N-二乙氨基]乙氧基]乙醇盐酸盐(T-588)是一种合成化合物,已知对神经细胞具有神经保护作用。在本研究中,使用大鼠模型评估了使用T-588进行新药治疗RLN损伤的可能性。
动物研究。
给动物施用T-588,持续4周。通过运动神经元细胞计数、胆碱乙酰转移酶免疫反应性评估、电生理检查和声带重新活动,研究了迷走神经撕脱后施用T-588的神经保护作用以及喉返神经挤压后的神经功能恢复情况。
施用T-588成功预防了迷走神经撕脱后同侧疑核中的运动神经元损失,并改善了胆碱乙酰转移酶免疫反应性。与对照组相比,治疗组的RLN运动神经传导速度和声带运动有显著改善。
这些结果表明,口服T-588可能是治疗周围神经损伤的一种有前景的治疗选择。