The Journal of Neuroscience, May 15, 2001, 21(10):3665-3673

Locomotor Recovery in Spinal Cord-Injured Rats Treated with an Antibody Neutralizing the Myelin-Associated Neurite Growth Inhibitor Nogo-A
Doron Merkler1, Gerlinde A.テつ*S. Metz2, Olivier Raineteau1, Volker Dietz3, Martin E. Schwab1, and Karim Fouad1, 3

1テつ*Department of Neuromorphology, Brain Research Institute, University and Swiss Federal Institute of Technology Zテδシrich, 8057テつ*Zテδシrich, Switzerland, 2テつ*Department of Psychology, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada, and 3テつ*Swiss Paraplegic Centre, University Hospital Balgrist, University of Zテδシrich, 8008テつ*Zテδシrich, Switzerland

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テつ*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テつ*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.

Key words: spinal cord injury; functional recovery; locomotion; Nogo-A; regeneration; plasticity; rats