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Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury

Nature Neuroscience volume 13, pages 1505–1510 (2010)Cite this article

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Abstract

Although axonal regeneration after CNS injury is limited, partial injury is frequently accompanied by extensive functional recovery. To investigate mechanisms underlying spontaneous recovery after incomplete spinal cord injury, we administered C7 spinal cord hemisections to adult rhesus monkeys and analyzed behavioral, electrophysiological and anatomical adaptations. We found marked spontaneous plasticity of corticospinal projections, with reconstitution of fully 60% of pre-lesion axon density arising from sprouting of spinal cord midline-crossing axons. This extensive anatomical recovery was associated with improvement in coordinated muscle recruitment, hand function and locomotion. These findings identify what may be the most extensive natural recovery of mammalian axonal projections after nervous system injury observed to date, highlighting an important role for primate models in translational disease research.

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Figure 1: Spontaneous improvement in object retrieval with the hand after C7 lateral hemisection.
Figure 2: Partial recovery in forelimb use during locomotion after C7 hemisection.
Figure 3: Extensive recovery of hindlimb locomotion after C7 hemisection.
Figure 4: Extensive compensatory plasticity of the lesioned corticospinal tract in primates.
Figure 5: Relationship between anatomical plasticity and functional recovery.

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Acknowledgements

The authors thank H. Yang, S. Zdunowski, M. Culbertson, H. Zhong, R. Moseanko, S. Hawbecker, H. McKay and T. Bernot for valuable experimental assistance. This work was supported by the US National Institutes of Health (NS42291, NS049881 and NS053059), the Veterans Administration, California Roman-Reed funds, the Bernard and Anne Spitzer Charitable Trust and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation.

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Author notes

  1. Ephron S Rosenzweig and Gregoire Courtine: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosciences, University of California San Diego, La Jolla, California, USA

    Ephron S Rosenzweig, John H Brock, Darren M Miller & Mark H Tuszynski

  2. Departments of Physiological Science and Neurology, University of California, Los Angeles, California, USA

    Gregoire Courtine, Devin L Jindrich, Roland R Roy, Leif A Havton & V Reggie Edgerton

  3. Department of Neurology, University of Zurich, Zurich, Switzerland

    Gregoire Courtine

  4. Department of Neurosurgery, University of California, San Francisco, California, USA

    Adam R Ferguson, Yvette S Nout, Michael S Beattie & Jacqueline C Bresnahan

  5. California National Primate Research Center, University of California, Davis, California, USA

    Sarah C Strand

  6. Veterans Administration Medical Center, La Jolla, California, USA

    Mark H Tuszynski

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  1. Ephron S Rosenzweig
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Contributions

E.S.R., G.C., M.S.B., L.A.H., J.C.B., V.R.E. and M.H.T. designed the study. S.C.S. tested experimental subjects. S.C.S., Y.S.N., G.C., D.L.J. and J.C.B. performed behavioral tests. M.H.T., E.S.R., R.R.R. and Y.S.N. performed surgeries. G.C., E.S.R., D.L.J. and A.R.F. analyzed behavioral, electrophysiological and kinematic data. E.S.R., J.H.B., D.M.M., L.A.H. and M.H.T. analyzed anatomical data. M.H.T., E.S.R. and G.C. wrote the manuscript. All of the authors discussed the results and commented on the manuscript.

Corresponding author

Correspondence to Mark H Tuszynski.

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The authors declare no competing financial interests.

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Supplementary Figures 1–11 and Supplementary Tables 1 and 2 (PDF 3130 kb)

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Rosenzweig, E., Courtine, G., Jindrich, D. et al. Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury. Nat Neurosci 13, 1505–1510 (2010). https://doi.org/10.1038/nn.2691

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