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Functional regeneration of sensory axons into the adult spinal cord

Nature volume 403, pages 312–316 (2000)Cite this article

Abstract

The arrest of dorsal root axonal regeneration at the transitional zone between the peripheral and central nervous system has been repeatedly described since the early twentieth century1. Here we show that, with trophic support to damaged sensory axons, this regenerative barrier is surmountable. In adult rats with injured dorsal roots, treatment with nerve growth factor (NGF), neurotrophin-3 (NT3) and glial-cell-line-derived neurotrophic factor (GDNF), but not brain-derived neurotrophic factor (BDNF), resulted in selective regrowth of damaged axons across the dorsal root entry zone and into the spinal cord. Dorsal horn neurons were found to be synaptically driven by peripheral nerve stimulation in rats treated with NGF, NT3 and GDNF, demonstrating functional reconnection. In behavioural studies, rats treated with NGF and GDNF recovered sensitivity to noxious heat and pressure. The observed effects of neurotrophic factors corresponded to their known actions on distinct subpopulations of sensory neurons. Neurotrophic factor treatment may thus serve as a viable treatment in promoting recovery from root avulsion injuries.

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Figure 1: Axonal growth across the dorsal root entry zone, one week post-lesion.
Figure 2: Functional reconnection of regenerating axons (A-fibre stimulation).
Figure 3: Functional reconnection of regenerating axons (high-intensity stimulation).
Figure 4: Behavioural recovery following rhizotomy.

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Acknowledgements

We thank E. Bradbury and T. Boucher for critical review of the manuscript, V. Cheah for technical assistance, and D. Shelton and Q. Yan for supplying neurotrophic factors. This work was supported by the European Union (S.B.M and J.V.P.) and a Prideaux grant from the Special Trustees of St. Thomas’ Hospital (S.B.M). M.S.R. receives a fellowship from the Medical Research Council of Canada.

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Authors and Affiliations

  1. Neuroscience Research Centre, Guy’s, King's and St. Thomas’ School of Biomedical Sciences, St. Thomas’ Campus, Lambeth Palace Road, London, SE1 7EH, UK

    Matt S. Ramer & Stephen B. McMahon

  2. Division of Biomedical Sciences, Neuroscience Section, Medical Sciences Building, Queen Mary and Westfield College, Mile End Road, London, E1 4NS, UK

    John V. Priestley

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Correspondence to Matt S. Ramer.

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Ramer, M., Priestley, J. & McMahon, S. Functional regeneration of sensory axons into the adult spinal cord. Nature 403, 312–316 (2000). https://doi.org/10.1038/35002084

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