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Nogo‐A antibody improves regeneration and locomotion of spinal cord–injured rats

Nogo‐A antibody improves regeneration and locomotion of spinal cord–injured rats Spinal cord trauma leads to loss of motor, sensory and autonomic functions below the lesion. Recovery is very restricted, due in part to neurite growth inhibitory myelin proteins, in particular Nogo‐A. Two neutralizing antibodies against Nogo‐A were used to study recovery and axonal regeneration after spinal cord lesions. Three months old Lewis rats were tested in sensory‐motor tasks (open field locomotion, crossing of ladder rungs and narrow beams, the CatWalk® runway, reactions to heat and von Frey hairs). A T‐shaped lesion was made at T8, and an intrathecal catheter delivered highly purified anti‐Nogo‐A monoclonal IgGs or unspecific IgGs for 2 weeks. A better outcome in motor behavior was obtained as early as two weeks after lesion in the animals receiving the Nogo‐A antibodies. Withdrawal responses to heat and mechanical stimuli were not different between the groups. Histology showed enhanced regeneration of corticospinal axons in the anti‐Nogo‐A antibody groups. fMRI revealed significant cortical responses to stimulation of the hindpaw exclusively in anti‐Nogo‐A animals. These results demonstrate that neutralization of the neurite growth inhibitor Nogo‐A by intrathecal antibodies leads to enhanced regeneration and reorganization of the injured CNS, resulting in improved recovery of compromised functions in the absence of dysfunctions. Ann Neurol 2005 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Neurology Wiley

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References (43)

Publisher
Wiley
Copyright
Copyright © 2003 American Neurological Association
ISSN
0364-5134
eISSN
1531-8249
DOI
10.1002/ana.20627
pmid
16173073
Publisher site
See Article on Publisher Site

Abstract

Spinal cord trauma leads to loss of motor, sensory and autonomic functions below the lesion. Recovery is very restricted, due in part to neurite growth inhibitory myelin proteins, in particular Nogo‐A. Two neutralizing antibodies against Nogo‐A were used to study recovery and axonal regeneration after spinal cord lesions. Three months old Lewis rats were tested in sensory‐motor tasks (open field locomotion, crossing of ladder rungs and narrow beams, the CatWalk® runway, reactions to heat and von Frey hairs). A T‐shaped lesion was made at T8, and an intrathecal catheter delivered highly purified anti‐Nogo‐A monoclonal IgGs or unspecific IgGs for 2 weeks. A better outcome in motor behavior was obtained as early as two weeks after lesion in the animals receiving the Nogo‐A antibodies. Withdrawal responses to heat and mechanical stimuli were not different between the groups. Histology showed enhanced regeneration of corticospinal axons in the anti‐Nogo‐A antibody groups. fMRI revealed significant cortical responses to stimulation of the hindpaw exclusively in anti‐Nogo‐A animals. These results demonstrate that neutralization of the neurite growth inhibitor Nogo‐A by intrathecal antibodies leads to enhanced regeneration and reorganization of the injured CNS, resulting in improved recovery of compromised functions in the absence of dysfunctions. Ann Neurol 2005

Journal

Annals of NeurologyWiley

Published: Nov 1, 2005

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