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      Extensive Spontaneous Plasticity of Corticospinal Projections After Primate Spinal Cord Injury

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          Abstract

          While 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, adult rhesus monkeys underwent C7 spinal cord hemisections, with subsequent analysis of behavioral, electrophysiological and anatomical adaptations. We found remarkable 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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          Most cited references28

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          The functional organization of the motor system in the monkey. I. The effects of bilateral pyramidal lesions.

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            Can experiments in nonhuman primates expedite the translation of treatments for spinal cord injury in humans?

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              Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury.

              Although it is believed that little recovery occurs after adult mammalian spinal cord injury, in fact significant spontaneous functional improvement commonly occurs after spinal cord injury in humans. To investigate potential mechanisms underlying spontaneous recovery, lesions of defined components of the corticospinal motor pathway were made in adult rats in the rostral cervical spinal cord or caudal medulla. Following complete lesions of the dorsal corticospinal motor pathway, which contains more than 95% of all corticospinal axons, spontaneous sprouting from the ventral corticospinal tract occurred onto medial motoneuron pools in the cervical spinal cord; this sprouting was paralleled by functional recovery. Combined lesions of both dorsal and ventral corticospinal tract components eliminated sprouting and functional recovery. In addition, functional recovery was also abolished if dorsal corticospinal tract lesions were followed 5 weeks later by ventral corticospinal tract lesions. We found extensive spontaneous structural plasticity as a mechanism correlating with functional recovery in motor systems in the adult central nervous system. Experimental enhancement of spontaneous plasticity may be useful to promote further recovery after adult central nervous system injury.
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                Author and article information

                Journal
                9809671
                21092
                Nat Neurosci
                Nature neuroscience
                1097-6256
                1546-1726
                19 November 2010
                14 November 2010
                December 2010
                27 July 2011
                : 13
                : 12
                : 1505-1510
                Affiliations
                [1 ]Dept. of Neurosciences, University of California - San Diego, La Jolla, CA
                [2 ]Depts. of Physiological Science and Neurology, University of California, Los Angeles, CA
                [3 ]Dept. of Neurology, University of Zurich, Zurich, Switzerland
                [4 ]Dept. of Neurosurgery, University of California, San Francisco, CA
                [5 ]California National Primate Research Center, University of California, Davis, CA
                [6 ]Veterans Administration Medical Center, La Jolla, CA
                Author notes
                [*]

                contributed equally to this work

                AUTHOR CONTRIBUTIONS ESR, GC, MSB, LAH, JCB, VRE, and MHT designed the study. SCS tested experimental subjects. SCS, YSN, GC, DLJ, and JCB performed behavioral tests. MHT, ESR, RRR, and YSN performed surgeries. GC, ESR, DLJ and ARF analyzed behavioral, electrophysiological, and kinematic data. ESR, JHB, DMM, LAH, and MHT analyzed anatomical data. MHT, ESR, and GC wrote the manuscript. All authors discussed the results and commented on the manuscript.

                Correspondence to: Mark H. Tuszynski, Dept. Neurosciences, 0626 University of California, San Diego, La Jolla, CA 92093 858-534-8857 858-534-5220 (fax) mtuszynski@ 123456ucsd.edu
                Article
                nihpa246996
                10.1038/nn.2691
                3144760
                21076427
                588d759a-a921-4ea9-bbda-cb5fd6d14df5

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                History
                Funding
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Award ID: R01 NS067092-02 ||NS
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Award ID: R01 NS049881-05 ||NS
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Award ID: R01 NS042291-09 ||NS
                Funded by: National Institute of Neurological Disorders and Stroke : NINDS
                Award ID: F32 NS053059-03 ||NS
                Categories
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                Neurosciences
                Neurosciences

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