Stimulation of denervated muscle promotes selective reinnervation, prevents synkinesis, and restores function.

Previously, electrical stimulation of denervated canine laryngeal muscle was shown to promote reinnervation by native over foreign motoneurons. The goal of this study was to assess the effect of different stimulus paradigms on reinnervation quality and functional recovery. A prospective study of six canines over 8 to 20 months. A clinical model of laryngeal paralysis was used, where recurrent laryngeal nerves of the animals were sectioned and ventilation compromised. The abductor, posterior cricoarytenoid (PCA) muscles were implanted bilaterally with electrodes from an implantable pulse generator. Animals were randomly assigned to three groups to assess the effect of different stimulus paradigms: 1) 40 pulses per second (pps) train, 2) 10 pps train, 3) no stimulation. Spontaneous vocal fold movement was measured endoscopically during hypercapnia. Exercise tolerance was measured on a treadmill using pulse oximetry. In the terminal session, electromyography (EMG) potentials were recorded during superior laryngeal nerve stimulation to index foreign reinnervation of the PCA by reflex glottic closure (RGC) motoneurons. After reinnervation started, nonstimulated and stimulated 40 pps animals displayed paradoxical closure of the glottis during hypercapnia and severely decreased exercise tolerance due to faulty reinnervation. In contrast, stimulated 10 pps animals displayed minimal paradoxical closure and normal exercise tolerance (12 minutes up to 8 mph). EMG findings in this group demonstrated significantly less PCA reinnervation by foreign RGC motoneurons. PCA stimulation with low frequency reduced synkinetic reinnervation by foreign RGC motoneurons. Paradoxical closure of the glottis with inspiration was reduced and exercise tolerance restored to normal.

Zealear DL ，Mainthia R ，Li Y ，Kunibe I ，Katada A ，Billante C ，Nomura K ... -  《-》

Electrical stimulation of a denervated muscle promotes selective reinnervation by native over foreign motoneurons.

Zealear DL ，Rodriguez RJ ，Kenny T ，Billante MJ ，Cho Y ，Billante CR ，Garren KC ... -  《-》

The effects of chronic electrical stimulation on laryngeal muscle reinnervation.

The present study examined the effects of functional neuromuscular stimulation (FNS) on reinnervation of the posterior cricoarytenoid (PCA) muscle. In 4 canines, the recurrent laryngeal nerve (RLN) was sectioned and anastomosed and a patch electrode array implanted for stimulation and recording at multiple PCA sites. Following implantation, FNS was applied to 2 canines for a period of 6 weeks. Two additional animals served as nonstimulated controls. In each animal, histomorphometric analysis of the RLN was used to assess the quality of nerve regeneration and the potential for muscle reconnection. The magnitude of reinnervation was monitored by electromyographic (EMG) potentials evoked by RLN stimulation. The appropriateness of reconnection was determined by the pattern of spontaneous EMG activity and recovery of vocal fold abduction. Results of this preliminary study indicated that FNS caused an overall repression of reinnervation. However, the repression preferentially inhibited reconnection by foreign nerve fibers, promoting selective reinnervation and preventing synkinesis.

Zealear DL ，Billante CL ，Chongkolwatana C ，Herzon GD ... -  《ORL-Journal for Oto-Rhino-Laryngology Head and Neck Surgery》

Physiologic motion after vocal cord reinnervation: a preliminary study.

Green DC ，Berke GS ，Graves MC ，Natividad M ... -  《-》

Embryologic innervation of the rat laryngeal musculature--a model for investigation of recurrent laryngeal nerve reinnervation.

Optimal management of vocal fold paralysis would entail recurrent laryngeal nerve (RLN) reinnervation resulting in normal vocal fold motion. Unfortunately, RLN reinnervation currently results in a nonfunctional vocal fold due to synkinetic reinnervation. Therapeutic interventions that guide regenerating axons back to the appropriate muscle would prevent synkinesis and restore vocal fold and glottal function. The initial step toward developing these therapies is the elucidation of the embryologic innervation of the larynx. This study aimed to identify the age of occurrence, timing, and pattern of embryologic innervation of the rat larynx, hypothesizing that differences in these parameters exist between distinct laryngeal muscles. Descriptive anatomic study. The larynx of rats aged embryologic day (E) 15, 16, 17, 19, and 21 were harvested and then sectioned. Two rats were used for each age. Sections were colabeled with neuronal class III β-tubulin polyclonal antibody to identify the presence of axons and alexa 488 conjugate α-bungarotoxin to identify the presence of motor endplates. The age at which axons and motor endplates were first present was noted. The position and pattern of the axons and motor endplates was recorded in relation to each other as well as the musculoskeletal anatomy of the larynx. The time at which axons appeared to innervate the medial thyroarytenoid (MTA) muscle, lateral thyroarytenoid (LTA) muscle, and the posterior cricoarytenoid (PCA) muscle was documented. Findings in the rat suggest the RLN reaches the larynx and begins branching by E15. Axons branch dorsally first and reach the PCA muscle before the other muscles. Branching toward the MTA muscle occurs only after axons have reached the LTA muscle. By E19, RLN axons have been guided to and selected their respective muscles with formation of neuromuscular junctions (NMJs) in the PCA, LTA and MTA muscles, though the formation of NMJs in the MTA muscle was comparatively delayed. This study describes the embryologic innervation of the rat larynx and suggests that there are distinct differences in the age of occurrence, timing, and pattern of innervation of the PCA, LTA, and MTA muscles of the rat. These findings lay the foundation for studies investigating the role of guidance cues in RLN axon guidance and the utility of these cues in the treatment of RLN injury via the stimulation of functional, nonsynkinetic reinnervation.

Pitman MJ ，Berzofsky CE ，Alli O ，Sharma S ... -  《-》