Regenerating corticospinal fibers in the Marmoset (Callitrix jacchus) after spinal cord lesion and treatment with the anti-Nogo-A antibody IN-1

Eur J Neurosci. 2004 Nov;20(9):2479-82. doi: 10.1111/j.1460-9568.2004.03716.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology*
  • Antibodies / therapeutic use
  • Antibodies, Monoclonal / pharmacology*
  • Callithrix
  • Cerebrospinal Fluid / metabolism
  • Female
  • Growth Cones / drug effects
  • Growth Cones / physiology
  • Growth Cones / ultrastructure
  • Hybridomas / metabolism
  • Hybridomas / transplantation
  • Male
  • Myelin Proteins / antagonists & inhibitors*
  • Myelin Proteins / metabolism
  • Nerve Regeneration / drug effects*
  • Nerve Regeneration / physiology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Nogo Proteins
  • Pyramidal Tracts / drug effects*
  • Pyramidal Tracts / injuries
  • Pyramidal Tracts / physiology
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / physiopathology
  • Spinal Cord Injuries / therapy*
  • Treatment Outcome

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Myelin Proteins
  • Nogo Proteins
  • RTN4 protein, human
  • Rtn4 protein, rat