4.5 Article

INVASION OF LESION TERRITORY BY REGENERATING FIBERS AFTER SPINAL CORD INJURY IN ADULT MACAQUE MONKEYS

Journal

NEUROSCIENCE
Volume 227, Issue -, Pages 271-282

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2012.09.052

Keywords

spinal cord lesion; scar tissue; primate; regeneration; BDNF; Nogo-A

Categories

Funding

  1. The Swiss National Science Foundation [31-43422.95, 31-61857.00, 310000-110005, 31003A-132465, 31-63633, 4038043918/2 (PNR-38), PZ00P3-121646, 3100A0-104061, 310000-118357]
  2. The National Centre of Competence in Research (NCCR) Neural plasticity and repair of the SNSF
  3. The Christopher Reeves Foundation Spinal Cord Consortium, (Springfield, NJ)
  4. Swiss National Science Foundation (SNF) [PZ00P3_121646] Funding Source: Swiss National Science Foundation (SNF)

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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 he application of an anti-Nogo-A antibody which otherwise festers 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 Weir trajectories were erratic. Most of these fibers (about 87%) were larger than 1.3 pm and densely SMI-32 (+) stained. In the undamaged spinal tissue, motoneurons form the only largo 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. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

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