Administration of monoclonal antibodies neutralizing the inflammatory mediators tumor necrosis factor alpha and interleukin -6 does not attenuate acute behavioral deficits following experimental traumatic brain injury in the rat
(2005) In Restorative Neurology and Neuroscience 23(1). p.31-42- Abstract
PURPOSE: Although many previous studies have indicated that the acute inflammatory response following traumatic brain injury (TBI) is detrimental, inflammation may also positively influence outcome in the more chronic post-injury recovery period. We evaluated the effects of monoclonal antibodies (mAB), neutralizing either IL-6 (IL-6 mAB) or TNF-alpha (TNF mAB), administered intracerebroventricularly (i.c.v) on acute neurobehavioral outcome following TBI.
METHODS: Male Sprague-Dawley rats (n = 173) were anesthetized (sodium pentobarbital, 60 mg/kg) and subjected to lateral fluid percussion (FP) brain injury of moderate severity (n = 123) or sham injury (n = 50). Beginning 1 h post-injury, TNF mAB (n = 41, of which 25 were... (More)
PURPOSE: Although many previous studies have indicated that the acute inflammatory response following traumatic brain injury (TBI) is detrimental, inflammation may also positively influence outcome in the more chronic post-injury recovery period. We evaluated the effects of monoclonal antibodies (mAB), neutralizing either IL-6 (IL-6 mAB) or TNF-alpha (TNF mAB), administered intracerebroventricularly (i.c.v) on acute neurobehavioral outcome following TBI.
METHODS: Male Sprague-Dawley rats (n = 173) were anesthetized (sodium pentobarbital, 60 mg/kg) and subjected to lateral fluid percussion (FP) brain injury of moderate severity (n = 123) or sham injury (n = 50). Beginning 1 h post-injury, TNF mAB (n = 41, of which 25 were brain-injured) or IL-6 mAB (n = 42, of which 25 were brain-injured) at a concentration of 2 mg/mL was infused i.c.v ipsilateral to the injury for 48 hours. Vehicle-treated animals (control IgG; n = 43, of which 26 were brain-injured) served as controls. In Study 1, cognitive function was evaluated in the Morris Water Maze (MWM) followed by evaluation of regional cerebral edema at 48 h post-injury. In Study 2, animals were evaluated for neurological motor function and post-injury learning in the MWM at one week post-injury.
RESULTS: FP brain injury caused significant cognitive (p < 0.05) and neurological motor (p < 0.05) deficits and increased regional brain water content in the injured hemisphere. Treatment with either TNF- or IL-6-mAB had no effect on neurological motor, cognitive function or brain edema during the first post-injury week.
CONCLUSIONS: Evaluation of anti-inflammatory mABs on more chronic behavioral deficits appears warranted.
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- author
- Marklund, Niklas LU ; Keck, Carrie ; Hoover, Rachel ; Soltesz, Kristie ; Millard, Marie ; LeBold, David ; Spangler, Zachary ; Banning, Adrian ; Benson, Jacqueline and McIntosh, Tracy K
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Antibodies, Monoclonal, Brain Edema, Brain Injuries, Cognition Disorders, Inflammation Mediators, Interleukin-6, Learning, Male, Motor Skills, Rats, Rats, Sprague-Dawley, Tumor Necrosis Factor-alpha, Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.
- in
- Restorative Neurology and Neuroscience
- volume
- 23
- issue
- 1
- pages
- 12 pages
- publisher
- IOS Press
- external identifiers
-
- scopus:20244371332
- pmid:15846030
- ISSN
- 0922-6028
- language
- English
- LU publication?
- no
- id
- f92ee1b0-fbd3-4d33-80a7-627ddc510a11
- date added to LUP
- 2016-12-08 12:17:36
- date last changed
- 2024-01-04 18:30:20
@article{f92ee1b0-fbd3-4d33-80a7-627ddc510a11, abstract = {{<p>PURPOSE: Although many previous studies have indicated that the acute inflammatory response following traumatic brain injury (TBI) is detrimental, inflammation may also positively influence outcome in the more chronic post-injury recovery period. We evaluated the effects of monoclonal antibodies (mAB), neutralizing either IL-6 (IL-6 mAB) or TNF-alpha (TNF mAB), administered intracerebroventricularly (i.c.v) on acute neurobehavioral outcome following TBI.</p><p>METHODS: Male Sprague-Dawley rats (n = 173) were anesthetized (sodium pentobarbital, 60 mg/kg) and subjected to lateral fluid percussion (FP) brain injury of moderate severity (n = 123) or sham injury (n = 50). Beginning 1 h post-injury, TNF mAB (n = 41, of which 25 were brain-injured) or IL-6 mAB (n = 42, of which 25 were brain-injured) at a concentration of 2 mg/mL was infused i.c.v ipsilateral to the injury for 48 hours. Vehicle-treated animals (control IgG; n = 43, of which 26 were brain-injured) served as controls. In Study 1, cognitive function was evaluated in the Morris Water Maze (MWM) followed by evaluation of regional cerebral edema at 48 h post-injury. In Study 2, animals were evaluated for neurological motor function and post-injury learning in the MWM at one week post-injury.</p><p>RESULTS: FP brain injury caused significant cognitive (p < 0.05) and neurological motor (p < 0.05) deficits and increased regional brain water content in the injured hemisphere. Treatment with either TNF- or IL-6-mAB had no effect on neurological motor, cognitive function or brain edema during the first post-injury week.</p><p>CONCLUSIONS: Evaluation of anti-inflammatory mABs on more chronic behavioral deficits appears warranted.</p>}}, author = {{Marklund, Niklas and Keck, Carrie and Hoover, Rachel and Soltesz, Kristie and Millard, Marie and LeBold, David and Spangler, Zachary and Banning, Adrian and Benson, Jacqueline and McIntosh, Tracy K}}, issn = {{0922-6028}}, keywords = {{Animals; Antibodies, Monoclonal; Brain Edema; Brain Injuries; Cognition Disorders; Inflammation Mediators; Interleukin-6; Learning; Male; Motor Skills; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}}, language = {{eng}}, number = {{1}}, pages = {{31--42}}, publisher = {{IOS Press}}, series = {{Restorative Neurology and Neuroscience}}, title = {{Administration of monoclonal antibodies neutralizing the inflammatory mediators tumor necrosis factor alpha and interleukin -6 does not attenuate acute behavioral deficits following experimental traumatic brain injury in the rat}}, volume = {{23}}, year = {{2005}}, }