Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti-myelin-associated glycoprotein antibody
Thompson, Hilaire J ; Marklund, Niklas LU
; LeBold, David G
; Morales, Diego M
; Keck, Carrie A
; Vinson, Mary
; Royo, Nicolas C
; Grundy, Robert
and McIntosh, Tracy K
(2006)
In European Journal of Neuroscience
24(11).
p.72-3063
- 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... (More)
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.
(Less)
- author
- Thompson, Hilaire J
; Marklund, Niklas
LU
; LeBold, David G
; Morales, Diego M
; Keck, Carrie A
; Vinson, Mary
; Royo, Nicolas C
; Grundy, Robert
and McIntosh, Tracy K
- publishing date
- 2006-12
- type
- Contribution to journal
- publication status
- published
- 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.
- in
- European Journal of Neuroscience
- volume
- 24
- issue
- 11
- pages
- 10 pages
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:17156367
- scopus:33845676295
- ISSN
- 0953-816X
- DOI
- 10.1111/j.1460-9568.2006.05197.x
- language
- English
- LU publication?
- no
- id
- d7b9df03-3de4-45c5-94db-96c91e835c38
- date added to LUP
- 2016-12-08 12:20:37
- date last changed
- 2024-02-19 12:45:57
@article{d7b9df03-3de4-45c5-94db-96c91e835c38,
abstract = {{<p>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.</p>}},
author = {{Thompson, Hilaire J and Marklund, Niklas and LeBold, David G and Morales, Diego M and Keck, Carrie A and Vinson, Mary and Royo, Nicolas C and Grundy, Robert and McIntosh, Tracy K}},
issn = {{0953-816X}},
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.}},
language = {{eng}},
number = {{11}},
pages = {{72--3063}},
publisher = {{Wiley-Blackwell}},
series = {{European Journal of Neuroscience}},
title = {{Tissue sparing and functional recovery following experimental traumatic brain injury is provided by treatment with an anti-myelin-associated glycoprotein antibody}},
url = {{http://dx.doi.org/10.1111/j.1460-9568.2006.05197.x}},
doi = {{10.1111/j.1460-9568.2006.05197.x}},
volume = {{24}},
year = {{2006}},
}