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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. S. Metz², Olivier Raineteau¹, Volker Dietz³, Martin E. Schwab¹, and Karim Fouad^{1, 3}

¹ Department of Neuromorphology, Brain Research Institute, University and Swiss Federal Institute of Technology Zürich, 8057 Zürich, Switzerland, ² Department of Psychology, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada, and ³ Swiss Paraplegic Centre, University Hospital Balgrist, University of Zürich, 8008 Zürich, 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 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.

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

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21103665-09$05.00/0

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