Locomotor recovery in spinal cord-injured rats treated with an antibody neutralizing the myelin-associated neurite growth inhibitor Nogo-A.
The limited plastic and regenerative capabilities of axons in the adult mammalian CNS can be enhanced by the application of a monoclonal antibody (mAb), IN-1, raised against the myelin-associated neurite growth inhibitor Nogo-A. The aim of the present study was to investigate the effects of this treatment on the functional recovery of adult rats with a dorsal over-hemisection of the spinal cord. Directly after injury, half of the animals were implanted with mAb IN-1-secreting hybridoma cells, whereas the others received cells secreting a control antibody (anti-HRP). A broad spectrum of locomotor tests (open field locomotor) score, grid walk, misstep withdrawal response, narrow-beam crossing) was used to characterize locomotor recovery during the 5 weeks after the injury. In all behavioral tests, the recovery in the mAb IN-1-treated group was significantly augmented compared with the control antibody-treated rats. EMG recordings of flexor and extensor muscles during treadmill walking confirmed the improvement of the locomotor pattern in the mAb IN-1-treated rats; step-cycle duration, rhythmicity, and coupling of the hindlimbs were significantly improved. No differences between the two groups with regard to nociception were observed in the tail flick test 5 weeks after the operation. These results indicating improved functional recovery suggest that the increased plastic and regenerative capabilities of the CNS after Nogo-A neutralization result in a functionally meaningful rewiring of the motor systems.
Merkler
D
D
Department of Neuromorphology, Brain Research Institute, University and Swiss Federal Institute of Technology Zürich, 8057 Zürich, Switzerland.
Metz
G A
GA
Raineteau
O
O
Dietz
V
V
Schwab
M E
ME
Fouad
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D019771:Axotomy; D001522:Behavior, Animal; D004195:Disease Models, Animal; D004576:Electromyography; D005260:Female; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors*; D006614:Hindlimb / Q000502:physiology; D008124:Locomotion; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009185:Myelin Proteins / Q000037:antagonists & inhibitors*; D016501:Neurites / Q000187:drug effects*; D000070798:Nogo Proteins; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D006131:Growth Inhibitors; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat