Rehabilitation of the Paralyzed Larynx

描述（由申请人提供）：功能性电刺激（FES）有望作为恢复失神经肌肉系统活动的治疗方法。最近在动物和患者中的研究表明，FES能够使瘫痪的喉外展肌恢复活力，保护它们在再生过程中免于萎缩，并促进选择性神经再支配。在本建议中，将进行两条研究路线，一条是应用研究，一条是基础研究。应用研究的总体目标是评估FES在植入电刺激装置的慢性双侧喉麻痹犬中恢复通气的能力。在这个模型中，声带外展肌肌肉将被刺激双侧恢复声门开放。将评估该器械在恢复通气方面的有效性和安全性。基础研究的总体目标是研究FES促进喉肌原运动神经元再支配的机制。有两种假说可以解释FES如何赋予神经肌肉特异性。第一种假设认为，电刺激维持了在发育过程中建立的运动神经元-肌肉纤维特异性，并防止其在去神经支配时的丧失。第二种假设认为肌肉可塑性的概念延伸到其突触，并且电刺激可以调节终板对特定类型运动神经元的感受性。这项研究将区分这两种假设。一组相关的实验将进行，以确定是否FES的选择性效果可以定位到神经或肌肉。最后，随着对提高展肌神经再支配质量的机制的理解，将检查在严重神经病变的情况下选择性地再支配和恢复自然功能的能力，以评估该方法与医学的临床相关性。总的来说，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最初可用于使单侧瘫痪的面部、喉和咽部恢复活力，并在此过程中直接自然地重新支配这些结构。

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.