Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti-myelin-associated glycoprotein antibody

Research output: Contribution to journalArticle


Axonal injury is a hallmark of traumatic brain injury (TBI) and is associated with a poor clinical outcome. Following central nervous system injury, axons regenerate poorly, in part due to the presence of molecules associated with myelin that inhibit axonal outgrowth, including myelin-associated glycoprotein (MAG). The involvement of MAG in neurobehavioral deficits and tissue loss following experimental TBI remains unexplored and was evaluated in the current study using an MAG-specific monoclonal antibody (mAb). Anesthetized rats (n=102) were subjected to either lateral fluid percussion brain injury (n=59) or sham injury (n=43). In surviving animals, beginning at 1 h post-injury, 8.64 microg anti-MAG mAb (n=33 injured, n=21 sham) or control IgG (n=26 injured, n=22 sham) was infused intracerebroventricularly for 72 h. One group of these rats (n=14 sham, n=11 injured) was killed at 72 h post-injury for verification of drug diffusion and MAG immunohistochemistry. All other animals were evaluated up to 8 weeks post-injury using tests for neurologic motor, sensory and cognitive function. Hemispheric tissue loss was also evaluated at 8 weeks post-injury. At 72 h post-injury, increased immunoreactivity for MAG was seen in the ipsilateral cortex, thalamus and hippocampus of brain-injured animals, and anti-MAG mAb was detectable in the hippocampus, fimbria and ventricles. Brain-injured animals receiving anti-MAG mAb showed significantly improved recovery of sensorimotor function at 6 and 8 weeks (P<0.01) post-injury when compared with brain-injured IgG-treated animals. Additionally, at 8 weeks post-injury, the anti-MAG mAb-treated brain-injured animals demonstrated significantly improved cognitive function and reduced hemispheric tissue loss (P<0.05) when compared with their brain-injured controls. These results indicate that MAG may contribute to the pathophysiology of experimental TBI and treatment strategies that target MAG may be suitable for further evaluation.


  • Hilaire J Thompson
  • Niklas Marklund
  • David G LeBold
  • Diego M Morales
  • Carrie A Keck
  • Mary Vinson
  • Nicolas C Royo
  • Robert Grundy
  • Tracy K McIntosh
External organisations
  • University of Pennsylvania
Research areas and keywords


  • Animals, Antibodies, Monoclonal, Axons, Brain, Brain Injuries, Demyelinating Diseases, Disease Models, Animal, Immunohistochemistry, Male, Myelin-Associated Glycoprotein, Nerve Regeneration, Rats, Rats, Sprague-Dawley, Recovery of Function, Treatment Outcome, Wallerian Degeneration, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
Original languageEnglish
Pages (from-to)3063-72
Number of pages10
JournalEuropean Journal of Neuroscience
Issue number11
Publication statusPublished - 2006 Dec
Publication categoryResearch
Externally publishedYes