Restoration of Recurrent-Laryngeal-Nerve Function after Injury in a Rat Model

大鼠模型损伤后喉返神经功能的恢复

• 批准号: 8960931
• 负责人: Richard Kollmar
• 金额: $ 20.19万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8960931
• 关键词: Accidental Injury; Action Potentials; Anastomosis - action; Animal Model; Animals; Axon; Basic Science; Breathing; Clinical; Complication; Connective Tissue; Crush Injury; Distal; Electromyography; FDA approved; Functional disorder; Future; Glycogen Synthase Kinase 3; Goals; Growth; Growth Cones; Head; Health; Human; Implant; In Vitro; Injury; Interdisciplinary Study; Intervention; Laboratories; Laryngeal muscle structure; Laryngoscopy; Larynx; Lesion; Lithium; Lithium Chloride; Methods; Modeling; Monitor; Mood Disorders; Morphology; Motion; Movement; Multi-Institutional Clinical Trial; Muscle; Muscle Tonus; Myelin; Natural regeneration; Neck; Nerve; Nerve Crush; Nerve Degeneration; Nerve Regeneration; Neurites; Operative Surgical Procedures; Paralysed; Pathway interactions; Patient observation; Patients; Peripheral nerve injury; Pharmacological Treatment; Pharmacotherapy; Physicians; Plethysmography; Procedures; Protocols documentation; Pump; Rattus; Recovery; Recurrent Laryngeal Nerve; Risk; Scientist; Series; Serum; Site; Stretching; Surgical Anastomosis; Synkinesis; Techniques; Testing; Thyroid Gland; Time; Transplantation; Trauma; Vocal Cord Paralysis; Voice; Water; axon regeneration; axonal sprouting; efficacy testing; extracellular; functional outcomes; implantation; improved; in vivo; injured; nerve injury; nerve transection; neurotrophic factor; operation; outcome forecast; pressure; reinnervation; repaired; restoration; sciatic nerve; tool; treatment group; vocal cord; vocalization

DESCRIPTION (provided by applicant): Unilateral vocal-fold paralysis is a major complication from thyroid surgery and commonly results from trauma to the recurrent laryngeal nerve (RLN). The loss of tone in the intrinsic muscles of the larynx due to RLN injury can eliminate voice, produce breathing difficulties, and significantly increase risk for aspiration. For crush injuries o the RLN, the only treatment is "watchful waiting" for spontaneous regeneration of axons and reinnervation of laryngeal muscles. For transected RLNs, the preferred treatment is surgical anastomosis of nerve segments followed by the same hopes for spontaneous regeneration and reinnervation. Both treatments can restore muscle tone, but reinnervation is inefficient and takes many months. Even then, purposeful movement of the vocal folds and complete glottic closure are not restored because of synkinesis from aberrant reinnervation, but, as long as there is reinnervation, laryngeal function can be further improved with surgical manipulation of laryngeal muscles. In this project, we will develop tools for producing controlled injury and test the efficacy of a simple, safe pharmacological treatment to significantly accelerate reinnervation. In Aim 1, we will develop quantitatively reproducible RLN crush injuries and quantitative techniques for the study of resulting vocal fold paralysis and functional reinnervation. In Aim 2, we will test the hypothesis that continuous lithium administration accelerates reinnervation after RLN crush injury. Lithium modulates glycogen synthase kinase 3 in the neurotrophin pathway and promotes growth-cone activity and neurite extension. For both aims, functional outcomes will be monitored at regular intervals by vocalization analysis, plethysmography, quantitative video laryngoscopy, and larynx electromyography. The results of this multidisciplinary collaboration between physicians and basic scientists will have direct practical clinical impact on the treatment of patients with unilateral vocal-fold paralysis. The quantitative tools for nerve injury and functional assessment, and the pharmacological treatment to accelerate axonal sprouting and reinnervation will have significant impact on all types of peripheral nerve injury.

描述（由申请人提供）：单方面声折叠瘫痪是甲状腺手术的主要并发症，通常是创伤到复发性喉神经（RLN）的主要并发症。由于RLN损伤而导致的喉部内在肌肉中的音调丧失可以消除声音，产生呼吸困难并显着增加抽吸的风险。对于RLN的压碎损伤，唯一的治疗方法是“注意等待”轴突自发再生和喉部肌肉的再生。对于跨性别的RLN，首选的治疗方法是神经段的手术吻合术，然后对自发再生和重新支配产生同样的希望。两种治疗方法都可以恢复肌肉张力，但加重作用效率低下，需要数月的时间。即使到那时，由于异常重新支配的合伙人，声带的有目的运动和完整的闭合闭合也无法恢复，但是，只要重新连接，喉部功能就可以通过手术操纵喉部的肌肉来进一步改善。 在这个项目中，我们将开发用于产生受控损伤的工具，并测试简单，安全的药理治疗以显着加快加剧的功效。在AIM 1中，我们将开发定量可重复的RLN压碎损伤和定量技术，以研究产生的声带瘫痪和功能连接。在AIM 2中，我们将检验以下假设：连续锂给药会加速RLN挤压损伤后加重作用。锂在神经营养途径中调节糖原合酶激酶3，并促进生长碳活性和神经突延伸。对于这两个目的，将通过发声分析，杂质图，定量视频喉镜和喉肌电图定期监测功能结果。 医师和基础科学家之间这种多学科合作的结果将对 单侧声折叠瘫痪患者的治疗。神经损伤和功能评估的定量工具以及加速轴突发芽和加重的药理治疗将对所有类型的周围神经损伤产生重大影响。