Regeneration of injured axons in the adult mammalian central nervous system.
The axons of peripheral nerves have a high capacity for regeneration after injury, whereas injury to the axons in the adult central nervous system (CNS) of higher species does not generally result in regeneration. In recent years, significant developments in neuroscience research have resulted in an improved understanding of the processes involved in the axonal response to CNS trauma. Myelin-associated proteins in the CNS white matter play a crucial role as strong inhibitors of the growth of nerve fibers. Neutralization of these proteins by monoclonal antibody IN-1 directed against the inhibitory proteins led to pronounced axonal regeneration in the adult spinal cords of lesioned rats. The morphological findings were recently complemented by the demonstration of very significant functional improvements in rats with transection lesions of their spinal cords after treatment with the antibody IN-1 that neutralizes the myelin-associated nerve growth inhibitors. Moreover, several neurotrophic factors that promote axonal survival and sprouting in the peripheral nervous system and the CNS have been identified in recent years. The combined use of specific neurotrophic factors and the IN-1 antibody in different experimental procedures, including spinal cord injury, have significantly improved regenerative axonal growth. We briefly review these recent developments in CNS axonal regeneration research and discuss possible clinical applications.
Tatagiba
M
M
Brain Research Institute, University of Zurich, Switzerland.
Brösamle
C
C
Schwab
M E
ME
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001369:Axons / Q000473:pathology / Q000502:physiology*; D006801:Humans; D009185:Myelin Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009414:Nerve Growth Factors / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology; D051381:Rats; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*
D000911:Antibodies, Monoclonal; D009185:Myelin Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins