Elsevier

Neuroscience

Volume 227, 27 December 2012, Pages 271-282
Neuroscience

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

https://doi.org/10.1016/j.neuroscience.2012.09.052Get rights and content
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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.

Highlights

► We examined the lesion territory in 18 macaque monkeys subjected to a cervical cord hemisection. ► Five monkeys received anti-Nogo-A antibody and BDNF, five only anti-Nogo-A and eight control antibody. ► The lesion territory was invaded with SMI-32-positive fibers, arising in majority from motoneurons. ► There was no difference in the number of SMI-32-positive fibers in the lesion territory in the three groups.

Abbreviations

BDNF
brain-derived neurotrophic factor
CS
corticospinal
CSPGs
chondroitin sulfate proteoglycans
PBS
phosphate-buffered saline
SMI-32
Sternberger monoclonal-incorporated antibody 32

Key words

spinal cord lesion
scar tissue
primate
regeneration
BDNF
Nogo-A

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