Nogo-66 receptor antagonist peptide (NEP1-40) administration promotes functional recovery and axonal growth after lateral funiculus injury in the adult rat
| Autor: | S. A. Rabacchi, Robert A. Kushner, Jed S. Shumsky, F. P. T. Hamers, Yang Cao, Marion Murray, Stephen M. Strittmatter, D. H. S. Lee, M. A. Sabol |
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| Přispěvatelé: | University of Groningen |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Pyramidal Tracts
Rats Sprague-Dawley Myelin Nogo Receptor 1 QUANTITATIVE GAIT ANALYSIS SPINAL-CORD-INJURY Axon Receptor Red Nucleus Neuronal Plasticity Myelin-associated glycoprotein Behavior Animal Chemistry General Medicine Receptor antagonist Denervation OVERGROUND LOCOMOTION Cell biology medicine.anatomical_structure Treatment Outcome INHIBITS NEURITE OUTGROWTH Female MYELIN-ASSOCIATED GLYCOPROTEIN CHRONIC CENTRAL PAIN Spinal Nerve Roots Myelin Proteins medicine.drug_class Growth Cones Receptors Cell Surface GPI-Linked Proteins TRACT REGENERATION Efferent Pathways Article medicine Animals NEP1-40 Spinal Cord Injuries CORTICOSPINAL AXONS CENTRAL-NERVOUS-SYSTEM Antagonist Recovery of Function rubrospinal tract Peptide Fragments spinal cord injury Nerve Regeneration Rats nervous system Raphe Nuclei Lateral funiculus Wallerian Degeneration MONOCLONAL-ANTIBODY IN-1 Neuroscience Rubrospinal tract |
| Zdroj: | Neurorehabilitation and neural repair, 22(3), 262-278. SAGE Publications Inc. |
| ISSN: | 1545-9683 |
| Popis: | Objective. The myelin protein Nogo inhibits axon regeneration by binding to its receptor (NgR) on axons. Intrathecal delivery of an NgR antagonist (NEP1-40) promotes growth of injured corticospinal axons and recovery of motor function following a dorsal hemisection. The authors used a similar design to examine recovery and repair after a lesion that interrupts the rubrospinal tract (RST). Methods. Rats received a lateral funiculotomy at C4 and NEP1-40 or vehicle was delivered to the cervical spinal cord for 4 weeks. Outcome measures included motor and sensory tests and immunohistochemistry. Results. Gait analysis showed recovery in the NEP1-40-treated group compared to operated controls, and a test of forelimb usage also showed a beneficial effect. The density of labeled RST axons increased ipsilaterally in the NEP1-40 group in the lateral funiculus rostral to the lesion and contralaterally in both gray and white matter. Thus, rubrospinal axons exhibited diminished dieback and/or growth up to the lesion site. This was accompanied by greater density of 5HT and calcitonin gene-related peptide axons adjacent to and into the lesion/matrix site in the NEP1-40 group. Conclusions. NgR blockade after RST injury is associated with axonal growth and/or diminished dieback of severed RST axons up to but not into or beyond the lesion/matrix site, and growth of serotonergic and dorsal root axons adjacent to and into the lesion/matrix site. NgR blockade also supported partial recovery of function. The authors' results indicate that severed rubrospinal axons respond to NEP1-40 treatment but less robustly than corticospinal, raphe-spinal, or dorsal root axons. |
| Databáze: | OpenAIRE |
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