Olfactory-ensheathing cells promote physiological repair of injured recurrent laryngeal nerves and functional recovery of glottises in dogs.

The aim of this study was to investigate whether the transplantation of olfactory-ensheathing cells (OECs) could physiologically repair severely injured recurrent laryngeal nerve (RLN) in dogs. Adult Beagle dogs were surgically introduced with a 10-mm defect in the left RLN and transplanted with a nerve guide (NEUROLAC) containing dog olfactory mucosa-olfactory-ensheathing cells (OM-OECs) in matrigel. The effects of OM-OECs on the morphology, histology, and electrophysiology of the injured RLNs, glottis movement, and voice acoustics were comparatively studied. Two months after transplantation, the normal dogs (group N) had intact left RLNs that contained axons well organized as bundles, transmitted action potentials of high amplitudes without latent phases, and modulated glottis movement to produce normal voices. The RLN-damaged dogs transplanted with OM-OECs (group CTT) had pieces of nerves regenerated in the place of the defects, which contained fewer axons scattered in the internal nerve membrane and wrapped peripherally by the connective tissue, prevented the distal trunk of the defected RLN from shrinking, transmitted action potentials of lower amplitudes with latent phases, and modulated a slightly impaired glottis movement to produce voices with slight differences compared to the N dogs. The RLN-damaged dogs without OM-OECs (group NC) had no nerves generated at the defective or the damaged area, leading to a shrinkage in the enervated distal nerve trunks; a blockage in nerve pulse transit; a paralysis of the left vocal cords; an impaired glottis movement; and abnormal voices. Transplantation of OM-OECs promoted nerve regeneration, and the recoveries of glottises and voices in dogs with RLN injury.

Changes in neurotrophic factors of adult rat laryngeal muscles during nerve regeneration.

Injury to the recurrent laryngeal nerve (RLN) leads to the loss of ipsilateral laryngeal fold movement, with dysphonia, and occasionally dysphagia. Functional movement of the vocal folds is never restored due to misrouting of regenerating axons to agonist and antagonist laryngeal muscles. Changes of neurotrophic factor expression within denervated muscles occur after nerve injury and may influence nerve regeneration, axon guidance and muscle reinnervation. This study investigates the expression of certain neurotrophic factors in the laryngeal muscles during the course of axonal regeneration using RT-PCR. The timing of neurotrophic factor expression was correlated to the reinnervation of the laryngeal muscles by motor axons. Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Netrin-1 (NTN-1) increased their expression levels in laryngeal muscles after nerve section and during regeneration of RLN. The upregulation of trophic factors returned to control levels following regeneration of RLN. The expression levels of the neurotrophic factors were correlated with the innervation of regenerating axons into the denervated muscles. The results suggest that certain neurotrophic factor expression is strongly correlated to the reinnervation pattern of the regenerating RLN. These factors may be involved in guidance and neuromuscular junction formation during nerve regeneration. In the future, their manipulation may enhance the selective reinnervation of the larynx.