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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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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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.
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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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DOI: https://doi.org/10.1038/nn.2691
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