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 mam malian CNS can be enhanced by the application of a monoclonal antibody (mAb ), IN- 1, raised against the myelin-associated neurite growth inhibitor Nog o- A. The aim of the present study was to investigate the effects of this t reatment on the functional recovery of adult rats with a dorsal overhemisec tion of the spinal cord. Directly after injury, half of the animals were im planted with mAb IN- 1- secreting hybridoma cells, whereas the others recei ved cells secreting a control antibody (anti- HRP). A broad spectrum of loc omotor tests (open field locomotor) score, grid walk, misstep withdrawal re sponse, 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 t he control antibody-treated rats. EMG recordings of flexor and extensor mus cles during treadmill walking confirmed the improvement of the locomotor pa ttern in the mAb IN- 1- treated rats; step- cycle duration, rhythmicity, an d coupling of the hindlimbs were significantly improved. No differences bet ween the two groups with regard to nociception were observed in the tail fl ick test 5 weeks after the operation. These results indicating improved fun ctional recovery suggest that the increased plastic and regenerative capabi lities of the CNS after Nogo- A neutralization result in a functionally mea ningful rewiring of the motor systems.