Repair of injured fiber tracts in the mammalian central nervous system

When fiber tracts are interrupted after an injury of the brain or spinal cord, the distal parts of the fibers degenerate and regeneration from the proximal stump is absent. Therefore, functional deficits as typically observed e.g. in paraplegia persist throughout life. Recent studies show that an initial attempt for regeneration is blocked by specific neurite growth inhibitory proteins and glycoproteins present in central nervous system (CNS) myelin and in the lesion scar. Antibodies that neutralize one of the most potent inhibitory constituents, Nogo-A, allow long-distance re-growth of injured axons in the rat and macaque spinal cord after injury, as well as enhanced compensatory growth of spared fiber tracts. These animals show a high degree of functional recovery for locomotion or hand function following large, incomplete spinal cord transections. Reagents to inactivate other inhibitory molecules and combined treatments for reduction of inhibition in myelin and scar as well as growth promoting factors will be applied in the future.