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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 ; 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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publishing date
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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
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
2017-01-01 08:42:38
@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},
  keyword      = {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},
}