Improving axonal growth and functional recovery after experimental spinal cord injury by neutralizing myelin associated inhibitors.
Injuries of the spinal cord often result in an irretrievable loss of motor and sensory functions of all body parts situated below the lesion site. Functional recovery is restricted mainly due to the limited regeneration and plasticity of injured axons in the adult central nervous system. Over the last few years different experimental approaches have led to axonal growth and functional benefits in animal models. This review focuses on the effects of the neutralization of myelin-associated neurite growth inhibitors, in particular Nogo-A, using the monoclonal antibody IN-1. Acute mAb IN-1 treatment of adult CNS lesioned rats results in extensive plastic changes of neuronal connections and regenerative fiber growth. In two different lesion paradigms (i.e. pyramidal tract lesion and incomplete spinal cord lesion in adult rats), the mAb IN-1-treated animals always showed a higher degree of recovery in various behavioral tests. These observations, together with electrophysiological results, suggest that neuronal CNS circuits of mAb IN-1-treated animals can be rearranged, and that sprouting and regenerating axons form functionally meaningful connections.
Fouad
K
K
Brain Research Institute, University of Zurich and Department of Biology ETH Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
Dietz
V
V
Schwab
M E
ME
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004195:Disease Models, Animal; D020439:Growth Cones / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D009185:Myelin Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects* / Q000276:immunology; D000070798:Nogo Proteins; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects* / Q000276:immunology; D013116:Spinal Cord / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603197:Rtn4 protein, rat