STUDIES IN LARYNGEAL DEVELOPMENT AND NERVE REGENERATION

急性喉返神经损伤的患者没有 不仅声带运动受损的功能后果，而且 沟通减少带来的心理影响。患有疾病的患者 单侧喉返神经损伤因失音和误吸而不同程度地丧失功能， 而双侧喉返神经损伤阻塞了呼吸道，因此有必要 气管切开术。这些情况往往是不适当的直接结果 喉肌肉再神经支配的轴突被错误地定向在 再生的过程。神经再支配的过程受 促进细胞黏附的表面分子。理想情况下，这个过程应该是 模拟轴突-轴突和轴突-的正常发育过程 肌肉连接是正确的。当正确的连接无法 发生残留性喉无力和功能障碍。 本研究的目的是确定运动单位的细胞变化。 对观察到的RLN神经支配模式负责的组织 大鼠喉部肌肉组织。拟议的研究延续了先前的工作， 表明喉部神经再支配的模式受 喉内收运动神经元对喉肌的优先接触 疑核。为进一步评价喉突的形态 在大鼠模型中，再生运动神经元将是 用逆行标记法按原始功能分类 技巧。细胞数量和体细胞大小将与代谢相关 用组织化学方法检测与神经损伤相关的改变 琥珀酸脱氢酶和细胞色素氧化酶。免疫细胞化学 将使用技术来评估细胞黏附的作用 分子在重新神经支配的过程中，特别是在 与喉运动神经元和肌肉功能有关的表达。 将比较修复过程中细胞黏附分子的表达模式 发生在正常发育的中枢和外周的事件 神经系统。 本CIDA的应用是基于所提出的研究和高级 发育神经生物学、免疫细胞化学、电子学方面的培训 显微镜和生物统计学。基本培训的目的是开发一个 以喉发育和机制为重点的应用研究计划 喉返神经再生。

The patient with acute recurrent laryngeal nerve (RLN) injury suffers not only the functional consequences of impaired vocal fold motion, but also the psychological impact of reduced communication. Patients with unilateral RLN injury are variably disabled by aphonia and aspiration, while bilateral RLN injuries obstruct the airway, thereby necessitating tracheotomy. These conditions are often the direct result of inappropriate reinnervation of laryngeal muscles by axons that are misdirected in the course of regeneration. The process of reinnervation is influenced by surface molecules that promote cell adhesion. Ideally, this process should simulate the normal developmental process wherein axon-axon and axon- muscle connections are made correctly. When proper connections fail to develop, residual laryngeal weakness and impairment of function occur. The purpose of this study is to define the cellular changes in motor unit organization responsible for observed patterns of RLN reinnervation of the rat laryngeal musculature. The proposed study continues earlier work which suggests that patterns of laryngeal reinnervation are subject to preferential contact of the laryngeal muscles by adductor motoneurons of the nucleus ambiguus. To further evaluate the process of laryngeal reinnervation in the rat model, regenerating motoneurons will be classified according to their original function using retrograde labeling techniques. Cell number and somatic size will be correlated with metabolic alterations associated with nerve injury using histochemical assays for succinic dehydrogenase and cytochrome oxidase. Immunocytochemistry techniques will be employed to evaluate the role of cell adhesion molecules in the process of reinnervation, specifically addressing expression with respect to laryngeal motoneuron and muscle function. Patterns of cell adhesion molecule expression in repair will be compared to the events occurring in the normal developing central and peripheral nervous system. This CIDA application is based on the proposed studies and advanced training in developmental neurobiology, immunocytochemistry, electron microscopy and biostatistics. The basic training is intended to develop an applied research program focused on laryngeal development and mechanisms of RLN regeneration.