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

Abstract

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.

• Authors: Hilaire J Thompson, Niklas Marklund, David G LeBold, Diego M Morales, Carrie A Keck, Mary Vinson, Nicolas C Royo, Robert Grundy, Tracy K McIntosh
• Journal: The European journal of neuroscience (Eur J Neurosci) Vol. 24 Issue 11 Pg. 3063-72 (Dec 2006) ISSN: 0953-816X [Print] France
• PMID: 17156367 (Publication Type: 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.)

Chemical References

• Antibodies, Monoclonal
• Myelin-Associated Glycoprotein

Topics

• Animals
• Antibodies, Monoclonal (immunology, pharmacology, therapeutic use)
• Axons (drug effects, immunology, pathology)
• Brain (drug effects, immunology, physiopathology)
• Brain Injuries (drug therapy, immunology, physiopathology)
• Demyelinating Diseases (drug therapy, immunology, physiopathology)
• Disease Models, Animal
• Immunohistochemistry
• Male
• Myelin-Associated Glycoprotein (antagonists & inhibitors, immunology)
• Nerve Regeneration (drug effects, immunology)
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (drug effects, immunology)
• Treatment Outcome
• Wallerian Degeneration (drug therapy, immunology, physiopathology)