Differential effects of anti-Nogo-A antibody treatment and treadmill training in rats with incomplete spinal cord injury.
Locomotor training on treadmills can improve recovery of stepping in spinal cord injured animals and patients. Likewise, lesioned rats treated with antibodies against the myelin associated neurite growth inhibitory protein, Nogo-A, showed increased regeneration, neuronal reorganization and behavioural improvements. A detailed kinematic analysis showed that the hindlimb kinematic patterns that developed in anti-Nogo-A antibody treated versus treadmill trained spinal cord injured rats were significantly different. The synchronous combined treatment group did not show synergistic effects. This lack of synergistic effects could not be explained by an increase in pain perception, sprouting of calcitonin gene-related peptide (CGRP) positive fibres or by interference of locomotor training with anti-Nogo-A antibody induced regeneration and sprouting of descending fibre tracts. The differential mechanisms leading to behavioural recovery during task-specific training and in regeneration or plasticity enhancing therapies have to be taken into account in designing combinatorial therapies so that their potential positive interactive effects can be fully expressed.
Brain Research Institute, Winterthurerstrasse 190, Zurich, Switzerland. imaier@hifo.uzh.ch
Irin C
IC
Maier
Ronaldo M
RM
Ichiyama
Grégoire
G
Courtine
Lisa
L
Schnell
Igor
I
Lavrov
V Reggie
VR
Edgerton
Martin E
ME
Schwab
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D006930:Hyperalgesia / Q000503:physiopathology; D009043:Motor Activity / Q000502:physiology; D009046:Motor Neurons / Q000378:metabolism; D009185:Myelin Proteins / Q000276:immunology*; D009416:Nerve Regeneration / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D000070798:Nogo Proteins; D011712:Pyramidal Tracts / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012701:Serotonin / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000534:rehabilitation / Q000628:therapy*
D000911:Antibodies, Monoclonal; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat; D012701:Serotonin