Chen, K, Marsh, BC, Cowan, M et al. (7 more authors) (2017) Sequential therapy of anti-Nogo-A antibody treatment and treadmill training leads to cumulative improvements after spinal cord injury in rats. Experimental Neurology, 292. pp. 135-144. ISSN 0014-4886
Abstract
Intense training is the most clinically successful treatment modality following incomplete spinal cord injuries (SCIs). With the advent of plasticity enhancing treatments, understanding how treatments might interact when delivered in combination becomes critical. Here, we investigated a rational approach to sequentially combine treadmill locomotor training with antibody mediated suppression of the fiber growth inhibitory protein Nogo-A. Following a large but incomplete thoracic lesion, rats were immediately treated with either anti-Nogo-A or control antibody (2 weeks) and then either left untrained or step-trained starting 3 weeks after injury for 8 weeks. It was found that sequentially combined therapy improved step consistency and reduced toe dragging and climbing errors, as seen with training and anti-Nogo-A individually. Animals with sequential therapy also adopted a more parallel paw position during bipedal walking and showed greater overall quadrupedal locomotor recovery than individual treatments. Histologically, sequential therapy induced the greatest corticospinal tract sprouting caudally into the lumbar region and increased the number of serotonergic synapses onto lumbar motoneurons. Increased primary afferent sprouting and synapse formation onto lumbar motoneurons observed with anti-Nogo-A antibody were reduced by training. Animals with sequential therapy also showed the highest reduction of lumbar interneuronal activity associated with walking (c-fos expression). No treatment effects for thermal nociception, mechanical allodynia, or lesion volume were observed. The results demonstrate that sequential administration of anti-Nogo-A antibody followed in time with intensive locomotor training leads to superior recovery of lost locomotor functions, which is probably mediated by changes in the interaction between descending sprouting and local segmental networks after SCI.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Elsevier Inc. This is an author produced version of a paper published in Experimental Neurology. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Locomotor training; Axonal sprouting; Corticospinal; 5-HT; Ia afferents; Exercise; c-Fos; Kinematics |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 22 Mar 2017 13:29 |
Last Modified: | 21 Mar 2018 01:38 |
Published Version: | https://doi.org/10.1016/j.expneurol.2017.03.012 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.expneurol.2017.03.012 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:114046 |