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

J Comp Neurol. 2007 Jun 1;502(4):644-59. doi: 10.1002/cne.21321.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antibodies / therapeutic use
  • Biotin / analogs & derivatives
  • Cell Count
  • Cell Size / drug effects
  • Dextrans
  • Female
  • Functional Laterality / physiology
  • Growth Cones / drug effects*
  • Growth Cones / immunology
  • Growth Cones / metabolism
  • Macaca fascicularis
  • Macaca mulatta
  • Male
  • Myelin Proteins / antagonists & inhibitors*
  • Myelin Proteins / metabolism
  • Nerve Degeneration / drug therapy
  • Nerve Degeneration / immunology
  • Nerve Degeneration / physiopathology
  • Nerve Regeneration / drug effects*
  • Nerve Regeneration / immunology
  • Nogo Proteins
  • Pyramidal Tracts / drug effects*
  • Pyramidal Tracts / immunology
  • Pyramidal Tracts / physiopathology
  • Recovery of Function / drug effects
  • Recovery of Function / immunology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / immunology
  • Spinal Cord Injuries / physiopathology
  • Treatment Outcome


  • Antibodies
  • Dextrans
  • Myelin Proteins
  • Nogo Proteins
  • biotinylated dextran amine
  • Biotin