Regenerating corticospinal fibers in the Marmoset (Callitrix jacchus) after spinal cord lesion and treatment with the anti-Nogo-A antibody IN-1.
Neutralizing the myelin-associated growth inhibitor Nogo-A in adult spinal cord-injured rats can promote regeneration of injured and compensatory sprouting of uninjured axons. Nogo-A is present in humans, making its neutralization a possible novel treatment option for paraplegic patients. In this study we examined the effects of an extensively used anti-Nogo-A antibody (mAb IN-1) on the regenerative capabilities of lesioned corticospinal tract (CST) axons in a primate, the Marmoset monkey. Unilateral thoracic lesions of the CST were performed in six adult Marmosets, followed by the application of mAb IN-1 into the cerebrospinal fluid circulation by a graft of hybridoma cells. A unilateral injection of biotin dextran amine into the motor cortex was performed to analyse sprouting and regeneration of the lesioned axons. In the control antibody-treated animal CST fibers stopped rostral to the lesion site and often showed retraction bulbs. In contrast, in four out of five mAb IN-1-treated animals fine labeled neurites had grown into, through and around the lesion site. Thus, this study provides first anatomical evidence that in primates, the neutralization of the myelin-associated inhibitor Nogo-A results in increased regenerative sprouting and growth of lesioned spinal cord axons.
Fouad
K
K
Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, T6G 2G4, Canada. karim.fouad@ualberta.ca
Klusman
I
I
Schwab
M E
ME
D000818:Animals; D000906:Antibodies / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002144:Callithrix; D002555:Cerebrospinal Fluid / Q000378:metabolism; D005260:Female; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D006825:Hybridomas / Q000378:metabolism / Q000637:transplantation; D008297:Male; D009185:Myelin Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D000070798:Nogo Proteins; D011712:Pyramidal Tracts / Q000187:drug effects* / Q000293:injuries / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome
D000906:Antibodies; D000911:Antibodies, Monoclonal; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603197:Rtn4 protein, rat