A novel drug therapy for recurrent laryngeal nerve injury using T-588
A novel drug therapy for recurrent laryngeal nerve injury using T-588
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DOI：
10.1097/mlg.0b013e31805f681f
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发表时间：
2007-07-01
期刊：
影响因子：
2.6
通讯作者：
Ogawa, Kaoru
中科院分区：
文献类型：
--
作者：
Mori, Yuko;Shiotani, Akihiro;Ogawa, Kaoru
目的/假设：我们以前已经表明，使用胰岛素样生长因子（IGF）-I，胶质细胞系源性神经营养因子（GDNF）和脑源性神经营养因子（BDNF），或这些营养因子的组合的基因治疗是喉返神经（RNL）麻痹的治疗选择。然而，仍然存在一些困难，阻止这种选择成为喉返神经损伤的常见临床治疗方法。因此，我们需要开发新的治疗选择，克服基因治疗的问题。R（-）-1-（苯并噻吩-5-基）-2-[2-N，N-二乙基氨基]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治疗喉返神经损伤的新药治疗的可能性。研究设计;动物研究。方法：动物给药T-588 4周。采用运动神经元计数、胆碱乙酰转移酶免疫反应性评价、电生理检查和声带再动员研究了迷走神经撕脱后T-588给药的神经保护作用和喉返神经挤压后的神经功能恢复。T型588给药成功地防止了运动神经元的丢失，并改善了胆碱乙酰转移酶在同侧疑核中的免疫反应性。迷走神经撕脱伤运动神经传导速度的RL和声带运动的显着改善，观察治疗组相比controls.Conclusion：这些结果表明，口服给药的T-588可能是一个有前途的治疗选择，在治疗周围神经损伤。
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 of recurrent laryngeal nerve (RNL) 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.Study Design; Animal study.Methods: 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.Results: 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 RL and vocal fold movement were observed in the treatment group when compared to controls.Conclusion: These results indicate that oral administration of T-588 might be a promising therapeutic option in treating peripheral nerve injury.