Fate of rubrospinal neurons after unilateral section of the cervical spinal cord in adult macaque monkeys: Effects of an antibody treatment neutralizing Nogo-A

Wannier-Morino, Patrizia; Schmidlin, Eric; Freund, Patrick; Belhaj-Saïf, Abderraouf; Bloch, Jocelyne; Mir, Anis K.; Rouiller, Eric M.; Wannier, Tierry

doi:10.1016/j.brainres.2007.11.019

Cited by 17 publications

(20 citation statements)

References 41 publications

(60 reference statements)

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“…Therefore, SMI-32 serves as a useful signal for rubrospinal neurons, especially for those in the caudal part. In a primate spinal cord injury study, SMI-32 antibody was used as a marker to label rubrospinal neurons (Wannier-Morino et al 2008). After unilateral section of the spinal cord, this study showed that the number of SMI-32-positive neurons was decreased.…”

Section: Anterograde Labelingmentioning

confidence: 99%

The red nucleus and the rubrospinal projection in the mouse

2011

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We studied the organization and spinal projection of the mouse red nucleus with a range of techniques (Nissl stain, immunofluorescence, retrograde tracer injections into the spinal cord, anterograde tracer injections into the red nucleus, and in situ hybridization) and counted the number of neurons in the red nucleus (3,200.9 ± 230.8). We found that the rubrospinal neurons were mainly located in the parvicellular region of the red nucleus, more lateral in the rostral part and more medial in the caudal part. Labeled neurons were least common in the rostral and caudal most parts of the red nucleus. Neurons projecting to the cervical cord were predominantly dorsomedially placed and neurons projecting to the lumbar cord were predominantly ventrolaterally placed. Immunofluorescence staining with SMI-32 antibody showed that ~60% of SMI-32-positive neurons were cervical cord-projecting neurons and 24% were lumbar cord-projecting neurons. SMI-32-positive neurons were mainly located in the caudomedial part of the red nucleus. A study of vGluT2 expression showed that the number and location of glutamatergic neurons matched with those of the rubrospinal neurons. In the anterograde tracing experiments, rubrospinal fibers travelled in the dorsal portion of the lateral funiculus, between the lateral spinal nucleus and the calretinin-positive fibers of the lateral funiculus. Rubrospinal fibers terminated in contralateral laminae 5, 6, and the dorsal part of lamina 7 at all spinal cord levels. A few fibers could be seen next to the neurons in the dorsolateral part of lamina 9 at levels of C8-T1 (hand motor neurons) and L5-L6 (foot motor neurons), which is consistent with a view that rubrospinal fibers may play a role in distal limb movement in rodents.

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Section: Anterograde Labelingmentioning

confidence: 99%

The red nucleus and the rubrospinal projection in the mouse

2011

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“…These animals were part of several studies on the consequences of anti-Nogo-A antibody treatment on the regeneration of CS axons as well as on behavioral recovery after cervical cord injury. Separate data from 10 of these animals have appeared in previous reports (Freund et al, 2006(Freund et al, , 2007(Freund et al, , 2009Beaud et al, 2008;Wannier-Morino et al, 2008). Surgery and care of the animals were in conformity to the Guide for the Care and Use of Laboratory Animals (ISBN 0-309-05377-3; and authorized by local Swiss veterinary authorities.…”

Section: Experimental Procedures Animalsmentioning

confidence: 99%

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

Beaud¹,

Rouiller²,

Bloch³

et al. 2012

Neuroscience

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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 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.

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“…30 -32 Schwab and colleagues subsequently developed an IgG anti-Nogo antibody for intrathecal application, which has been shown in rat and primate models of SCI to promote axonal sprouting and behavioral improvements. [33][34][35][36] This anti-Nogo IgG intrathecal approach has been commercialized by Novartis, who sponsored the initiation of an open label, nonrandomized human clinical trial currently being conducted as a multicenter study across Europe and in Canada (ClinicalTrials.gov Identifier: NCT00406016). SCI.…”

Section: Anti-nogo Antibodiesmentioning

confidence: 99%