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Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation

Nature Neuroscience volume 12, pages 1145–1151 (2009)Cite this article

Abstract

Chondroitinase ABC treatment promotes spinal cord plasticity. We investigated whether chondroitinase-induced plasticity combined with physical rehabilitation promotes recovery of manual dexterity in rats with cervical spinal cord injuries. Rats received a C4 dorsal funiculus cut followed by chondroitinase ABC or penicillinase as a control. They were assigned to two alternative rehabilitation procedures, the first reinforcing skilled reaching and the second reinforcing general locomotion. Chondroitinase treatment enhanced sprouting of corticospinal axons independently of the rehabilitation regime. Only the rats receiving the combination of chondroitinase and specific rehabilitation showed improved manual dexterity. Rats that received general locomotor rehabilitation were better at ladder walking, but had worse skilled-reaching abilities than rats that received no treatment. Our results indicate that chondroitinase treatment opens a window during which rehabilitation can promote recovery. However, only the trained skills are improved and other functions may be negatively affected.

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Figure 1: ChABC or penicillinase (Pen) without rehabilitation.
Figure 2: To study CSPG digestion after ChABC treatment, we killed a set of rats by perfusion the day after the last intrathecal injection.
Figure 3
Figure 4: Effects of task-specific rehabilitation.
Figure 5: Effects of general rehabilitation.
Figure 6: Corticospinal axonal plasticity.

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Acknowledgements

The authors acknowledge key advice and assistance from H. Steenson in animal care and testing. This work was funded by grants from the Medical Research Council, The Wellcome Trust, The Christopher and Dana Reeve Foundation Consortium, The EU Framework 6 Network of Excellence NeuroNE, the Henry Smith Charity and Action Medical Research.

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Authors and Affiliations

  1. Department of Clinical Neuroscience, Centre for Brain Repair, University of Cambridge, Cambridge, UK

    Guillermo García-Alías, Stanley Barkhuysen, Miranda Buckle & James W Fawcett

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  1. Guillermo García-Alías
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  4. James W Fawcett
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Contributions

G.G.-A. and J.W.F. designed the experiments. G.G.-A., S.B. and M.B. performed the experiments. G.G.-A. and J.W.F. analyzed the data and wrote the paper.

Corresponding author

Correspondence to James W Fawcett.

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Competing interests

James W Fawcett is a paid consultant for Acorda Therapeutics and Alseres Pharmaceuticals.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7 (PDF 2860 kb)

Supplementary Video 1

Animal's performance in Whishaw's skilled paw reaching apparatus. (MOV 399 kb)

Supplementary Video 2

Task-specific and general rehabilitation therapies. (MOV 200 kb)

Supplementary Video 3

Animal's performance in the staircase. (MOV 444 kb)

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García-Alías, G., Barkhuysen, S., Buckle, M. et al. Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat Neurosci 12, 1145–1151 (2009). https://doi.org/10.1038/nn.2377

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