Effect of neurotrophin‐3 on reinnervation of the larynx using the phrenic nerve transfer technique

Abstract

Current techniques for reinnervation of the larynx following recurrent laryngeal nerve (RLN) injury are limited by synkinesis, which prevents functional recovery. Treatment with neurotrophins (NT) may enhance nerve regeneration and encourage more accurate reinnervation. This study presents the results of using the phrenic nerve transfer method, combined with NT-3 treatment, to selectively reinnervate the posterior cricoarytenoid (PCA) abductor muscle in a pig nerve injury model. RLN transection altered the phenotype and morphology of laryngeal muscles. In both the PCA and thyroarytenoid (TA) adductor muscle, fast type myosin heavy chain (MyHC) protein was decreased while slow type MyHC was increased. These changes were accompanied with a significant reduction in muscle fibre diameter. Following nerve repair there was a progressive normalization of MyHC phenotype and increased muscle fibre diameter in the PCA but not the TA muscle. This correlated with enhanced abductor function indicating the phrenic nerve accurately reinnervated the PCA muscle. Treatment with NT-3 significantly enhanced phrenic nerve regeneration but led to only a small increase in the number of reinnervated PCA muscle fibres and minimal effect on abductor muscle phenotype and morphology. Therefore, work exploring other growth factors, either alone or in combination with NT-3, is required.

Neurotrophic factor‐secreting autologous muscle stem cell therapy for the treatment of laryngeal denervation injury

“…These in vitro investigations demonstrated CNTF to have greater survival‐promoting effects on the MSCs than any of the other factors tested, which is consistent with our previous in vivo study that demonstrated the addition of CNTF at the time of MSC injection in a denervated rat hemilarynx (TA) led to greater MSC survival when compared to other trophic factors 17. No previous studies have investigated therapeutic CNTF delivery for RLN injury, although multiple investigations have studied the effects of other neurotrophic factors such as IGF‐1 and neurotrophin‐3 on RLN regeneration 12–14, 26. Because CNTF had not been previously studied for RLN injury, the motoneuron assays described in the Experiments to Address Specific Aim 1B section were essential to determine if CNTF at physiologic concentrations would have a positive effect on CNX motoneuron outgrowth.…”

Helicoid end‐to‐side and oblique attachment technique in repair of the musculocutaneous nerve injury with the phrenic nerve as a donor: An experimental study in rats

“…Along with brachial plexus injuries, the phrenic nerve has been used as a donor nerve to improve laryngeal function. In 2007, Kingham et al reported excellent results using phrenic nerve transfer for reinnervation of the larynx 9…”

Airway tissue engineering

“…Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) have all shown promise in speeding up peripheral nerve repair and are presently being applied in models of laryngeal reinnervation [90]. Important areas to be investigated are which growth factors to use when, and how to retain them at the repair site [91,92].…”