Invasion of lesion territory by regenerating fibers after spinal cord injury in adult macaque monkeys

Neuroscience. 2012 Dec 27;227:271-82. doi: 10.1016/j.neuroscience.2012.09.052. Epub 2012 Oct 2.

Abstract

In adult macaque monkeys subjected to an incomplete spinal cord injury (SCI), corticospinal (CS) fibers are rarely observed to grow in the lesion territory. This situation is little affected by the application of an anti-Nogo-A antibody which otherwise fosters the growth of CS fibers rostrally and caudally to the lesion. However, when using the Sternberger monoclonal-incorporated antibody 32 (SMI-32), a marker detecting a non-phosphorylated neurofilament epitope, numerous SMI-32-positive (+) fibers were observed in the spinal lesion territory of 18 adult macaque monkeys; eight of these animals had received a control antibody infusion intrathecally for 1 month after the injury, five animals an anti-Nogo-A antibody, and five animals received an anti-Nogo-A antibody together with brain-derived neurotrophic factor (BDNF). These fibers occupied the whole dorso-ventral axis of the lesion site with a tendency to accumulate on the ventral side, and their trajectories were erratic. Most of these fibers (about 87%) were larger than 1.3 μm and densely SMI-32 (+) stained. In the undamaged spinal tissue, motoneurons form the only large population of SMI-32 (+) neurons which are densely stained and have large diameter axons. These data therefore suggest that a sizeable proportion of the fibers seen in the lesion territory originate from motoneurons, although fibers of other origins could also contribute. Neither the presence of the antibody neutralizing Nogo-A alone, nor the presence of the antibody neutralizing Nogo-A combined with BDNF influenced the number or the length of the SMI-32 (+) fibers in the spinal lesion area. In summary, our data show that after a spinal cord lesion in adult monkeys, the lesion site is colonized by fibers, a large portion of which presumably originate from motoneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / therapeutic use
  • Brain-Derived Neurotrophic Factor / therapeutic use
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Disease Models, Animal
  • Female
  • Injections, Spinal
  • Macaca
  • Male
  • Myelin Proteins / immunology*
  • Myelin Proteins / metabolism
  • Nerve Fibers / drug effects
  • Nerve Fibers / physiology*
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / physiology*
  • Neurofilament Proteins / metabolism
  • Nogo Proteins
  • Recovery of Function / drug effects
  • Recovery of Function / physiology*
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / pathology*
  • Spinal Cord Injuries / physiopathology

Substances

  • Antibodies
  • Brain-Derived Neurotrophic Factor
  • Chondroitin Sulfate Proteoglycans
  • Myelin Proteins
  • Neurofilament Proteins
  • Nogo Proteins