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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

Marklund, Niklas LU orcid ; Keck, Carrie ; Hoover, Rachel ; Soltesz, Kristie ; Millard, Marie ; LeBold, David ; Spangler, Zachary ; Banning, Adrian ; Benson, Jacqueline and McIntosh, Tracy K (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
; ; ; ; ; ; ; ; and
publishing date
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
  • pmid:15846030
  • scopus:20244371332
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 &lt; 0.05) and neurological motor (p &lt; 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}},
}