Immunization with myelin or recombinant Nogo-66/MAG in alum promotes axon regeneration and sprouting after corticospinal tract lesions in the spinal cord

Mol Cell Neurosci. 2003 Jun;23(2):251-63. doi: 10.1016/s1044-7431(03)00053-8.

Abstract

We have shown previously that immunization with myelin in incomplete Freund's adjuvant (IFA) is able to promote robust regeneration of corticospinal tract fibers in adult mice. In the present study the effectiveness of such immunization with myelin was compared to that of a combination of two axon growth inhibitors in myelin, Nogo-66 (the 66-amino-acid inhibitory region of Nogo-A) and myelin-associated glycoprotein (MAG). The effectiveness of two adjuvants, IFA and aluminum hydroxide (Alum), was also compared, the latter being one that can be used in humans. In addition, larger dorsal overhemisections were made at the lower thoracic level, which resulted in a larger scar. These studies were carried out in SJL/J mice, a mouse strain that is susceptible to autoimmune experimental allergic encephalomyelitis (EAE). None of the immunized mice developed EAE. Long-distance axon regeneration and sprouting of the corticospinal tract was seen in myelin and Nogo-66/MAG immunized mice. Alum was as effective or better than IFA as the adjuvant. Overall, the robustness of axon growth and sprouting was greater in mice immunized with myelin. The abundance of this growth was less than in our earlier work in which smaller lesions were made, pointing to the possible influence of inhibitors in the scar. This work shows, however, that axon growth inhibitors in myelin can be selectively blocked using this immunization approach to promote long-distance axon regeneration in the spinal cord.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum Hydroxide / pharmacology
  • Animals
  • Female
  • Freund's Adjuvant / pharmacology
  • Growth Cones / drug effects
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Immunotherapy / methods
  • Immunotherapy / trends
  • Lipids*
  • Mice
  • Mice, Inbred Strains
  • Myelin Proteins / immunology
  • Myelin Proteins / pharmacology*
  • Myelin Proteins / therapeutic use
  • Myelin Sheath / immunology*
  • Myelin Sheath / metabolism
  • Myelin-Associated Glycoprotein / immunology
  • Myelin-Associated Glycoprotein / pharmacology*
  • Myelin-Associated Glycoprotein / therapeutic use
  • Nerve Fibers, Myelinated / immunology
  • Nerve Fibers, Myelinated / metabolism
  • Nerve Fibers, Myelinated / ultrastructure
  • Nerve Regeneration / genetics
  • Nerve Regeneration / immunology*
  • Nogo Proteins
  • Pyramidal Tracts / drug effects
  • Pyramidal Tracts / growth & development
  • Pyramidal Tracts / injuries*
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / immunology
  • Treatment Outcome

Substances

  • Lipids
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Nogo Proteins
  • RTN4 protein, human
  • Rtn4 protein, mouse
  • incomplete Freund's adjuvant
  • Aluminum Hydroxide
  • Freund's Adjuvant