title: 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.
authors.affiliation: Blond McIndoe Research Laboratories, Plastic and Reconstructive Surgery Research, Stopford Building, University of Manchester, Oxford Road, Manchester, M13 9PT, UK. paul.j.kingham@manchester.ac.uk
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kingham
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hughes
authors.forename: Louisa
authors.initials: L
authors.lastname: Mitchard
authors.forename: Rachel
authors.initials: R
authors.lastname: Burt
authors.forename: Pamela
authors.initials: P
authors.lastname: Murison
authors.forename: Alan
authors.initials: A
authors.lastname: Jones
authors.forename: Giorgio
authors.initials: G
authors.lastname: Terenghi
authors.forename: Martin A
authors.initials: MA
authors.lastname: Birchall
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004576:Electromyography; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D007818:Laryngeal Diseases / Q000188:drug therapy / Q000601:surgery; D007821:Laryngeal Muscles / Q000294:innervation* / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D007823:Laryngeal Nerves / Q000601:surgery*; D018995:Myosin Heavy Chains / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology*; D020933:Neurotrophin 3 / Q000627:therapeutic use*; D010791:Phrenic Nerve / Q000601:surgery*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D012009:Recurrent Laryngeal Nerve / Q000601:surgery; D013552:Swine; D013556:Swine, Miniature; D046608:Synkinesis / Q000503:physiopathology; D013997:Time Factors
chemical_list: D020933:Neurotrophin 3; D018995:Myosin Heavy Chains