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

Authors

  • Paul J. Kingham,

    1. Blond McIndoe Research Laboratories, Plastic and Reconstructive Surgery Research, Stopford Building, University of Manchester, Oxford Road, Manchester, M13 9PT, UK
    2. Laryngeal Research Group, University of Bristol, Langford House, Langford, UK
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  • Alexandra Hughes,

    1. Blond McIndoe Research Laboratories, Plastic and Reconstructive Surgery Research, Stopford Building, University of Manchester, Oxford Road, Manchester, M13 9PT, UK
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  • Louisa Mitchard,

    1. Laryngeal Research Group, University of Bristol, Langford House, Langford, UK
    2. Department of Clinical Veterinary Science, University of Bristol, Langford House, Langford, UK
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  • Rachel Burt,

    1. Laryngeal Research Group, University of Bristol, Langford House, Langford, UK
    2. Department of Clinical Veterinary Science, University of Bristol, Langford House, Langford, UK
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  • Pamela Murison,

    1. Laryngeal Research Group, University of Bristol, Langford House, Langford, UK
    2. Department of Clinical Veterinary Science, University of Bristol, Langford House, Langford, UK
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  • Alan Jones,

    1. Laryngeal Research Group, University of Bristol, Langford House, Langford, UK
    2. Department of Clinical Veterinary Science, University of Bristol, Langford House, Langford, UK
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  • Giorgio Terenghi,

    1. Blond McIndoe Research Laboratories, Plastic and Reconstructive Surgery Research, Stopford Building, University of Manchester, Oxford Road, Manchester, M13 9PT, UK
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  • Martin A. Birchall

    1. Laryngeal Research Group, University of Bristol, Langford House, Langford, UK
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Dr Paul Kingham, 1Blond McIndoe Research Laboratories, as above.
E-mail: paul.j.kingham@manchester.ac.uk

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.

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