Neutralization of interleukin-1beta modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice
Clausen, Fredrik ; Hånell, Anders ; Björk, Maria ; Hillered, Lars ; Mir, Anis K ; Gram, Hermann and Marklund, Niklas LU
(2009)
In European Journal of Neuroscience
30(3).
p.96-385
- Abstract
Interleukin-1beta (IL-1beta) may play a central role in the inflammatory response following traumatic brain injury (TBI). We subjected 91 mice to controlled cortical impact (CCI) brain injury or sham injury. Beginning 5 min post-injury, the IL-1beta neutralizing antibody IgG2a/k (1.5 microg/mL) or control antibody was infused at a rate of 0.25 microL/h into the contralateral ventricle for up to 14 days using osmotic minipumps. Neutrophil and T-cell infiltration and microglial activation was evaluated at days 1-7 post-injury. Cognition was assessed using Morris water maze, and motor function using rotarod and cylinder tests. Lesion volume and hemispheric tissue loss were evaluated at 18 days post-injury. Using this treatment strategy,... (More)
Interleukin-1beta (IL-1beta) may play a central role in the inflammatory response following traumatic brain injury (TBI). We subjected 91 mice to controlled cortical impact (CCI) brain injury or sham injury. Beginning 5 min post-injury, the IL-1beta neutralizing antibody IgG2a/k (1.5 microg/mL) or control antibody was infused at a rate of 0.25 microL/h into the contralateral ventricle for up to 14 days using osmotic minipumps. Neutrophil and T-cell infiltration and microglial activation was evaluated at days 1-7 post-injury. Cognition was assessed using Morris water maze, and motor function using rotarod and cylinder tests. Lesion volume and hemispheric tissue loss were evaluated at 18 days post-injury. Using this treatment strategy, cortical and hippocampal tissue levels of IgG2a/k reached 50 ng/mL, sufficient to effectively inhibit IL-1betain vitro. IL-1beta neutralization attenuated the CCI-induced cortical and hippocampal microglial activation (P < 0.05 at post-injury days 3 and 7), and cortical infiltration of neutrophils (P < 0.05 at post-injury day 7). There was only a minimal cortical infiltration of activated T-cells, attenuated by IL-1beta neutralization (P < 0.05 at post-injury day 7). CCI induced a significant deficit in neurological motor and cognitive function, and caused a loss of hemispheric tissue (P < 0.05). In brain-injured animals, IL-1beta neutralizing treatment resulted in reduced lesion volume, hemispheric tissue loss and attenuated cognitive deficits (P < 0.05) without influencing neurological motor function. Our results indicate that IL-1beta is a central component in the post-injury inflammatory response that, in view of the observed positive neuroprotective and cognitive effects, may be a suitable pharmacological target for the treatment of TBI.
(Less)
- author
- Clausen, Fredrik
; Hånell, Anders
; Björk, Maria
; Hillered, Lars
; Mir, Anis K
; Gram, Hermann
and Marklund, Niklas
LU
- publishing date
- 2009-08
- type
- Contribution to journal
- publication status
- published
- keywords
- Animals, Brain Injuries, Cognition, Image Processing, Computer-Assisted, Immunohistochemistry, Inflammation, Interleukin-1beta, Male, Maze Learning, Mice, Mice, Inbred C57BL, Microglia, Neutrophil Infiltration, Rotarod Performance Test, T-Lymphocytes, Journal Article, Research Support, Non-U.S. Gov't
- in
- European Journal of Neuroscience
- volume
- 30
- issue
- 3
- pages
- 96 - 385
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:19614750
- scopus:68249103676
- ISSN
- 1460-9568
- DOI
- 10.1111/j.1460-9568.2009.06820.x
- language
- English
- LU publication?
- no
- id
- 69265970-b1af-4a52-ab60-46774bcb186a
- date added to LUP
- 2018-03-03 14:59:19
- date last changed
- 2024-04-15 04:04:14
@article{69265970-b1af-4a52-ab60-46774bcb186a,
abstract = {{<p>Interleukin-1beta (IL-1beta) may play a central role in the inflammatory response following traumatic brain injury (TBI). We subjected 91 mice to controlled cortical impact (CCI) brain injury or sham injury. Beginning 5 min post-injury, the IL-1beta neutralizing antibody IgG2a/k (1.5 microg/mL) or control antibody was infused at a rate of 0.25 microL/h into the contralateral ventricle for up to 14 days using osmotic minipumps. Neutrophil and T-cell infiltration and microglial activation was evaluated at days 1-7 post-injury. Cognition was assessed using Morris water maze, and motor function using rotarod and cylinder tests. Lesion volume and hemispheric tissue loss were evaluated at 18 days post-injury. Using this treatment strategy, cortical and hippocampal tissue levels of IgG2a/k reached 50 ng/mL, sufficient to effectively inhibit IL-1betain vitro. IL-1beta neutralization attenuated the CCI-induced cortical and hippocampal microglial activation (P < 0.05 at post-injury days 3 and 7), and cortical infiltration of neutrophils (P < 0.05 at post-injury day 7). There was only a minimal cortical infiltration of activated T-cells, attenuated by IL-1beta neutralization (P < 0.05 at post-injury day 7). CCI induced a significant deficit in neurological motor and cognitive function, and caused a loss of hemispheric tissue (P < 0.05). In brain-injured animals, IL-1beta neutralizing treatment resulted in reduced lesion volume, hemispheric tissue loss and attenuated cognitive deficits (P < 0.05) without influencing neurological motor function. Our results indicate that IL-1beta is a central component in the post-injury inflammatory response that, in view of the observed positive neuroprotective and cognitive effects, may be a suitable pharmacological target for the treatment of TBI.</p>}},
author = {{Clausen, Fredrik and Hånell, Anders and Björk, Maria and Hillered, Lars and Mir, Anis K and Gram, Hermann and Marklund, Niklas}},
issn = {{1460-9568}},
keywords = {{Animals; Brain Injuries; Cognition; Image Processing, Computer-Assisted; Immunohistochemistry; Inflammation; Interleukin-1beta; Male; Maze Learning; Mice; Mice, Inbred C57BL; Microglia; Neutrophil Infiltration; Rotarod Performance Test; T-Lymphocytes; Journal Article; Research Support, Non-U.S. Gov't}},
language = {{eng}},
number = {{3}},
pages = {{96--385}},
publisher = {{Wiley-Blackwell}},
series = {{European Journal of Neuroscience}},
title = {{Neutralization of interleukin-1beta modifies the inflammatory response and improves histological and cognitive outcome following traumatic brain injury in mice}},
url = {{http://dx.doi.org/10.1111/j.1460-9568.2009.06820.x}},
doi = {{10.1111/j.1460-9568.2009.06820.x}},
volume = {{30}},
year = {{2009}},
}