Nogo-A antibodies and training reduce muscle spasms in spinal cord-injured rats.
OBJECTIVE
Spinal cord injury (SCI) leads to permanent motor and sensory deficits due to the damage of ascending and descending fiber tracts. In addition, malfunctions such as neuropathic pain or muscle spasms develop in many patients, possibly caused by injury-induced plastic changes of neuronal circuits above and below the lesion. New treatment strategies for spinal cord injury aim at enhancing plasticity and neurite growth, for example, by blocking the key neurite growth inhibitor Nogo-A or its downstream effectors. It is therefore crucial to investigate potential effects of such treatments on malfunctions such as muscle spasms. In addition, locomotor training, now a standard therapeutic tool to improve walking ability in incomplete SCI subjects, can be expected to influence the rearrangement of spinal cord circuits and the development of muscle spasms and other malfunctions.


RESULTS
Here we present and validate a new rat model for muscle spasms after incomplete SCI and show that both intrathecal anti-Nogo-A antibody treatment and locomotor training, started early after injury, permanently reduce the development of muscle spasms.


CONCLUSIONS
The results show that an antibody-mediated suppression of the growth inhibitory protein Nogo-A leads to functional recovery and a lower level of malfunctions, suggesting the formation of functionally meaningful connections in the damaged spinal cord. Treadmill training early after SCI also has a beneficial effect.
Gonzenbach
Roman R
RR
Brain Research Institute, University of Zurich, Winterthurerstrasse 190, Zurich, Switzerland. r.gonzenbach@gmail.com
Gasser
Pascal
P
Zörner
Björn
B
Hochreutener
Eva
E
Dietz
Volker
V
Schwab
Martin E
ME
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D008124:Locomotion; D009185:Myelin Proteins / Q000276:immunology*; D000070798:Nogo Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D013035:Spasm / Q000209:etiology / Q000517:prevention & control*; D013119:Spinal Cord Injuries / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat