Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti-myelin-associated glycoprotein antibody
2006 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 24, no 11, 3063-3072 p.Article in journal (Refereed) Published
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 mu g 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.
Place, publisher, year, edition, pages
2006. Vol. 24, no 11, 3063-3072 p.
adhesive/sticky paper test, head injury, hemispheric tissue loss, myelin-associated glycoprotein, osmotic minipumps, rat
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-146547DOI: 10.1111/j.1460-9568.2006.05197.xISI: 000243361700010PubMedID: 17156367OAI: oai:DiVA.org:uu-146547DiVA: diva2:398405