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Anti-Nogo-A antibody treatment enhances sprouting of corticospinal axons rostral to a unilateral cervical spinal cord lesion in adult macaque monkey

Authors

  • Patrick Freund,

    1. Unit of Physiology and Program in Neurosciences, Department of Medicine, Faculty of Sciences, University of Fribourg, CH-1700 Fribourg, Switzerland
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    • The first three authors contributed equally to this work.

  • Thierry Wannier,

    1. Unit of Physiology and Program in Neurosciences, Department of Medicine, Faculty of Sciences, University of Fribourg, CH-1700 Fribourg, Switzerland
    2. Brain Research Institute, Department of Neuromorphology, University and ETH Zurich, CH-8057 Zürich, Switzerland
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    • The first three authors contributed equally to this work.

  • Eric Schmidlin,

    1. Unit of Physiology and Program in Neurosciences, Department of Medicine, Faculty of Sciences, University of Fribourg, CH-1700 Fribourg, Switzerland
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    • The first three authors contributed equally to this work.

  • Jocelyne Bloch,

    1. Department of Neurosurgery, Neurosurgery Clinic, University Hospital of Lausanne, CH-1011 Lausanne, Switzerland
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  • Anis Mir,

    1. Novartis Institute for Biomedical Research, CH-4002 Basel, Switzerland
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  • Martin E. Schwab,

    1. Brain Research Institute, Department of Neuromorphology, University and ETH Zurich, CH-8057 Zürich, Switzerland
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  • Eric M. Rouiller

    Corresponding author
    1. Unit of Physiology and Program in Neurosciences, Department of Medicine, Faculty of Sciences, University of Fribourg, CH-1700 Fribourg, Switzerland
    • Unit of Physiology, Department of Medicine, University of Fribourg, Chemin du Musée 5, CH-1700 Fribourg, Switzerland
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Abstract

After injury, regrowth of axons in mammalian adult central nervous system is highly limited. However, in monkeys subjected to unilateral cervical lesion (C7–C8 level), neutralization of an important neurite outgrowth inhibitor, Nogo-A, stimulated axonal sprouting caudal to the lesion, accompanied by enhanced functional recovery of manual dexterity, compared with lesioned monkeys treated with a control antibody (Freund et al. [2006] Nat. Med. 12:790–792). The present study aimed at comparing the same two groups of monkeys for axonal sprouting rostral to the cervical lesion. The corticospinal tract was labeled by injecting the anterograde tracer biotinylated dextran amine into the contralesional motor cortex. The corticospinal axons were interrupted at the level of the lesion, accompanied by retrograde axonal degeneration (axon dieback), reflected by the presence of terminal retraction bulbs. The number of terminal retraction bulbs was lower in anti-Nogo-A antibody treated monkeys, and, when present, they were found closer to the lesion than in control-antibody treated monkeys. Compared with control antibody treated monkeys, the anti-Nogo-A antibody treated monkeys exhibited an increased cumulated axon arbor length and a higher number of axon arbors going in the medial direction from the white to the gray matter. Higher in the cervical cord (at C5 level), the anti-Nogo-A treatment enhanced the number of corticospinal fibers crossing the midline, suggesting axonal sprouting. Thus, the anti-Nogo-A antibody treatment enhanced axonal sprouting rostral to the cervical lesion; some of these fibers grew around the lesion and into the caudal spinal segments. These processes paralleled the observed improved functional recovery. J. Comp. Neurol. 502:644–659, 2007. © 2007 Wiley-Liss, Inc.

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