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Chondroitinase ABC promotes functional recovery after spinal cord injury

Author

Listed:
  • Elizabeth J. Bradbury

    (Hodgkin Building, Kings College London, Guy's Campus)

  • Lawrence D. F. Moon

    (University of Cambridge
    Miami Project to Cure Paralysis)

  • Reena J. Popat

    (Hodgkin Building, Kings College London, Guy's Campus)

  • Von R. King

    (St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary, University of London)

  • Gavin S. Bennett

    (Hodgkin Building, Kings College London, Guy's Campus)

  • Preena N. Patel

    (Hodgkin Building, Kings College London, Guy's Campus)

  • James W. Fawcett

    (University of Cambridge)

  • Stephen B. McMahon

    (Hodgkin Building, Kings College London, Guy's Campus)

Abstract

The inability of axons to regenerate after a spinal cord injury in the adult mammalian central nervous system (CNS) can lead to permanent paralysis. At sites of CNS injury, a glial scar develops, containing extracellular matrix molecules including chondroitin sulphate proteoglycans (CSPGs)1,2. CSPGs are inhibitory to axon growth in vitro3,4,5, and regenerating axons stop at CSPG-rich regions in vivo6. Removing CSPG glycosaminoglycan (GAG) chains attenuates CSPG inhibitory activity7,8,9,10. To test the functional effects of degrading chondroitin sulphate (CS)-GAG after spinal cord injury, we delivered chondroitinase ABC (ChABC) to the lesioned dorsal columns of adult rats. We show that intrathecal treatment with ChABC degraded CS-GAG at the injury site, upregulated a regeneration-associated protein in injured neurons, and promoted regeneration of both ascending sensory projections and descending corticospinal tract axons. ChABC treatment also restored post-synaptic activity below the lesion after electrical stimulation of corticospinal neurons, and promoted functional recovery of locomotor and proprioceptive behaviours. Our results demonstrate that CSPGs are important inhibitory molecules in vivo and suggest that their manipulation will be useful for treatment of human spinal injuries.

Suggested Citation

  • Elizabeth J. Bradbury & Lawrence D. F. Moon & Reena J. Popat & Von R. King & Gavin S. Bennett & Preena N. Patel & James W. Fawcett & Stephen B. McMahon, 2002. "Chondroitinase ABC promotes functional recovery after spinal cord injury," Nature, Nature, vol. 416(6881), pages 636-640, April.
    • Handle: RePEc:nat:nature:v:416:y:2002:i:6881:d:10.1038_416636a
    DOI: 10.1038/416636a
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    Cited by:

    1. Julia Kolb & Vasiliki Tsata & Nora John & Kyoohyun Kim & Conrad Möckel & Gonzalo Rosso & Veronika Kurbel & Asha Parmar & Gargi Sharma & Kristina Karandasheva & Shada Abuhattum & Olga Lyraki & Timon Be, 2023. "Small leucine-rich proteoglycans inhibit CNS regeneration by modifying the structural and mechanical properties of the lesion environment," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    2. Floriane Bretheau & Adrian Castellanos-Molina & Dominic Bélanger & Maxime Kusik & Benoit Mailhot & Ana Boisvert & Nicolas Vallières & Martine Lessard & Matthias Gunzer & Xiaoyu Liu & Éric Boilard & Ni, 2022. "The alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    3. Wei Li & Jian Chen & Shujie Zhao & Tianhe Huang & Huiyan Ying & Claudia Trujillo & Giuseppina Molinaro & Zheng Zhou & Tao Jiang & Wei Liu & Linwei Li & Yuancheng Bai & Peng Quan & Yaping Ding & Jouni , 2022. "High drug-loaded microspheres enabled by controlled in-droplet precipitation promote functional recovery after spinal cord injury," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Shannon Trombley & Jackson Powell & Pavithran Guttipatti & Andrew Matamoros & Xiaohui Lin & Tristan O’Harrow & Tobias Steinschaden & Leann Miles & Qin Wang & Shuchao Wang & Jingyun Qiu & Qingyang Li &, 2023. "Glia instruct axon regeneration via a ternary modulation of neuronal calcium channels in Drosophila," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    5. Vishnu Muraleedharan Saraswathy & Lili Zhou & Mayssa H. Mokalled, 2024. "Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    6. Isaac Francos-Quijorna & Marina Sánchez-Petidier & Emily R. Burnside & Smaranda R. Badea & Abel Torres-Espin & Lucy Marshall & Fred Winter & Joost Verhaagen & Victoria Moreno-Manzano & Elizabeth J. Br, 2022. "Chondroitin sulfate proteoglycans prevent immune cell phenotypic conversion and inflammation resolution via TLR4 in rodent models of spinal cord injury," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    7. Myungsik Yoo & Muntasir Khaled & Kurt M Gibbs & Jonghun Kim & Björn Kowalewski & Thomas Dierks & Melitta Schachner, 2013. "Arylsulfatase B Improves Locomotor Function after Mouse Spinal Cord Injury," PLOS ONE, Public Library of Science, vol. 8(3), pages 1-12, March.

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