Regeneration and sprouting of chronically injured corticospinal tract fibers in adult rats promoted by NT-3 and the mAb IN-1, which neutralizes myelin-associated neurite growth inhibitors.
Myelin-associated inhibitors of neurite growth play an important role in the regenerative failure after injury in the adult mammalian CNS. The application of the mAb IN-1, which efficiently neutralizes the NI-250/35 inhibitory proteins, alone or in combination with neurotrophin-3 (NT-3), has been shown to promote axonal regeneration when applied in acute injury models. To test whether IN-1 application can induce axonal growth also in a chronic injury model, we treated rats with IN-1 and NT-3 starting 2 or 8 weeks after injury. Rats underwent bilateral dorsal hemisection of the spinal cord at the age of 5-6 weeks. Regeneration of corticospinal (CST) fibers into the caudal spinal cord was observed in three of eight of those animals with a 2-week delay between lesion and treatment. CST fibers regenerated for 2-11.4 mm. In the control group sprouting occurred rostral to the lesion but no long-distance regeneration occurred. In animals where treatment started at 8 weeks after injury the longest fibers observed grew up to 2 mm into the caudal spinal cord. The results show that transected corticospinal axons retain the ability to regenerate at least for a few weeks after injury. Functional analysis of these animals showed a slight improvement of functional recovery.
von Meyenburg
J
J
Brain Research Institute, University of Zürich and Swiss Federal Institute of Technology, Zurich, Switzerland.
Brösamle
C
C
Metz
G A
GA
Schwab
M E
ME
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006614:Hindlimb / Q000502:physiology; D008124:Locomotion / Q000187:drug effects; D009185:Myelin Proteins / Q000276:immunology*; D009413:Nerve Fibers, Myelinated / Q000502:physiology / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D016501:Neurites / Q000502:physiology; D020933:Neurotrophin 3; D011712:Pyramidal Tracts / Q000166:cytology / Q000293:injuries*; D051381:Rats; D011917:Rats, Inbred Lew
D000911:Antibodies, Monoclonal; D009185:Myelin Proteins; D009414:Nerve Growth Factors; D020933:Neurotrophin 3