Rehabilitation of the Paralyzed Larynx

描述(由申请人提供)：功能性电刺激(FES)有望成为恢复失神经肌肉系统活动的一种治疗方法。最近在动物和患者身上的研究表明，FES能够使瘫痪的喉展肌恢复活力，保护它们在再生过程中免受萎缩，并促进选择性神经再支配。在本提案中，将进行两项研究，一项是应用研究，一项是基础研究。这项应用研究的总体目标是评估FES在植入电刺激装置后恢复慢性双侧喉麻痹犬呼吸的能力。在这个模型中，双侧声带外展肌将被刺激以恢复声门开放。将评估该装置在恢复通风方面的有效性和安全性。基础研究的总体目标是研究FES通过其原始运动神经元促进喉肌再神经支配的机制。有两个假说可以解释FES是如何赋予神经肌肉特异性的。第一种假说认为，电刺激保持了在发育过程中建立的运动神经元-肌肉纤维的特异性，并防止了它在失神经时的丧失。第二种假设假设肌肉可塑性的概念延伸到它的突触，电刺激可以调节终板对特定类型运动神经元的感受性。拟议的研究将区分这两个假设。将进行一系列相关实验，以确定FES的选择性效应是否可以局限于神经或肌肉。最后，在了解了提高外展肌再神经支配质量的机制后，将检查在发生严重神经损伤的情况下选择性重新神经支配和恢复自然功能的能力，以评估这种药物治疗方法的临床相关性。总体而言，FES在其他电机系统中的潜在应用是无限的。对于头部和颈部，FES最初可用于复活单侧瘫痪的面、喉和咽，并在此过程中直接对这些结构进行自然神经支配。

DESCRIPTION (provided by applicant): Functional electrical stimulation (FES) has promise as a therapy for restoring activity to a denervated muscle system. Recent studies in animals and patients have demonstrated the capacity for FES to reanimate paralyzed laryngeal abductor muscles, protect them from atrophy during regeneration, and promote selective reinnervation. In the present proposal, two lines of research, one applied and one basic, will be conducted. The overall goal of the applied research is to evaluate the capacity of FES to restore ventilation in canines with chronic bilateral laryngeal paralysis, implanted with electrical stimulation devices. In this model, the vocal fold abductor muscles will be stimulated bilaterally to reanimate glottal opening. The efficacy and safety of the device in restoring ventilation will be assessed. The overall goal of the basic research is to investigate the mechanisms by which FES facilitates reinnervation of a laryngeal muscle by its original motoneurons. Two hypotheses that could explain how FES confers neuromuscular specificity have been proposed. The first hypothesis holds that electrical stimulation maintains the motoneuron-muscle fiber specificity that was established during development, and prevents its loss upon denervation. The second hypothesis assumes that the concept of muscle plasticity extends to its synapse, and that electrical stimulation can modulate receptivity of the endplate for a particular type of motoneuron. The proposed research will distinguish between these two hypotheses. A set of related experiments will be performed to determine whether the selective effect of FES can be localized to either the nerve or muscle. Finally, with an understanding of the mechanisms for enhancing the quality of abductor muscle reinnervation, the capacity to selectively reinnervate and restore natural function in case of serious nerve lesions will be examined, to assess the clinical relevance of the approach to medicine. In general, the potential application of FES to other motor systems is limitless. With respect to the head and neck, FES could be employed initially to reanimate the unilaterally paralyzed face, larynx and pharynx, and in the process, direct natural reinnervation of these structures.