Effect of NT-4 and BDNF delivery to damaged sciatic nerves on phenotypic recovery of fast and slow muscles fibres

  1. Magda Simon1,
  2. Rebecca Porter2,
  3. Robert Brown2,
  4. Gary R. Coulton3,
  5. Giorgio Terenghi4

Article first published online: 10 NOV 2003

DOI: 10.1046/j.1460-9568.2003.02978.x

Issue

European Journal of Neuroscience

European Journal of Neuroscience

Volume 18, Issue 9, pages 2460–2466, November 2003

Additional Information

How to Cite

Simon, M., Porter, R., Brown, R., Coulton, G. R. and Terenghi, G. (2003), Effect of NT-4 and BDNF delivery to damaged sciatic nerves on phenotypic recovery of fast and slow muscles fibres. European Journal of Neuroscience, 18: 2460–2466. doi: 10.1046/j.1460-9568.2003.02978.x

Author Information

  1. 1

    Blond McIndoe Centre, Royal Free and University College Medical School, London, UK

  2. 2

    Tissue Engineering and Repair Centre, RFUCMS, Institute of Orthopaedics, Stanmore, Middlesex, UK

  3. 3

    Department Basic Medical Sciences and Department Cardiological Sciences, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK

  4. 4

    Blond McIndoe Research Laboratories, The University of Manchester, Manchester, UK

* : Dr Gary Coulton, as above. E-mail: g.coulton@sghms.ac.uk

Publication History

  1. Issue published online: 10 NOV 2003
  2. Article first published online: 10 NOV 2003
  3. Received 27 May 2003, revised 1 August 2003, accepted 5 August 2003

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Keywords:

  • BDNF;
  • muscle fibre;
  • nerve regeneration;
  • neurotrophin;
  • NT4;
  • trk B receptor

Abstract

We investigated whether neurotrophin-4 (NT-4) and brain-derived neurotrophic factor (BDNF) affected the reinnervation of slow and fast motor units. Neurotrophin-impregnated or plain fibronectin (FN) conduits were inserted into a sciatic nerve gap. Fast extensor digitorum longus (EDL) and slow soleus muscles were collected 4 months postsurgery. Muscles were weighed and fibre type proportion and mean fibre diameters were derived from muscle cross-sections. All fibre types in muscles from FN animals were severely atrophied and this correlated well with type 1 fibre loss and atrophy in soleus and type 2b loss and atrophy in EDL. Treatment with NT-4 reversed soleus but not EDL mass loss above the FN group by significantly restoring type 1 muscle fibre proportion and diameters towards those of normal unoperated animals. BDNF did not increase muscle mass but did have minor effects on fibre type and diameter. Thus, NT-4 significantly improved slow motor unit recovery, and provides a basis for therapies intended to aid the functional recovery of muscles after denervating injury.

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