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 overhemisection 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.