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Traumatic axonal injury in the mouse is accompanied by a dynamic inflammatory response, astroglial reactivity and complex behavioral changes

Ekmark-Lewén, Sara; Flygt, Johanna; Kiwanuka, Olivia; Meyerson, Bengt J; Lewén, Anders; Hillered, Lars and Marklund, Niklas LU (2013) In Journal of Neuroinflammation 10. p.1-19
Abstract

BACKGROUND: Diffuse traumatic axonal injury (TAI), a common consequence of traumatic brain injury, is associated with high morbidity and mortality. Inflammatory processes may play an important role in the pathophysiology of TAI. In the central fluid percussion injury (cFPI) TAI model in mice, the neuroinflammatory and astroglial response and behavioral changes are unknown.

METHODS: Twenty cFPI-injured and nine sham-injured mice were used, and the neuroinflammatory and astroglial response was evaluated by immunohistochemistry at 1, 3 and 7 days post-injury. The multivariate concentric square field test (MCSF) was used to compare complex behavioral changes in mice subjected to cFPI (n = 16) or sham injury (n = 10). Data was analyzed... (More)

BACKGROUND: Diffuse traumatic axonal injury (TAI), a common consequence of traumatic brain injury, is associated with high morbidity and mortality. Inflammatory processes may play an important role in the pathophysiology of TAI. In the central fluid percussion injury (cFPI) TAI model in mice, the neuroinflammatory and astroglial response and behavioral changes are unknown.

METHODS: Twenty cFPI-injured and nine sham-injured mice were used, and the neuroinflammatory and astroglial response was evaluated by immunohistochemistry at 1, 3 and 7 days post-injury. The multivariate concentric square field test (MCSF) was used to compare complex behavioral changes in mice subjected to cFPI (n = 16) or sham injury (n = 10). Data was analyzed using non-parametric statistics and principal component analysis (MCSF data).

RESULTS: At all post-injury time points, β-amyloid precursor protein (β-APP) immunoreactivity revealed widespread bilateral axonal injury and IgG immunostaining showed increased blood-brain barrier permeability. Using vimentin and glial fibrillary acidic protein (GFAP) immunohistochemistry, glial cell reactivity was observed in cortical regions and important white matter tracts peaking at three days post-injury. Only vimentin was increased post-injury in the internal capsule and only GFAP in the thalamus. Compared to sham-injured controls, an increased number of activated microglia (MAC-2), infiltrating neutrophils (GR-1) and T-cells (CD3) appearing one day after TAI (P<0.05 for all cell types) was observed in subcortical white matter. In the MCSF, the behavioral patterns including general activity and exploratory behavior differed between cFPI mice and sham-injured controls.

CONCLUSIONS: Traumatic axonal injury TAI resulted in marked bilateral astroglial and neuroinflammatory responses and complex behavioral changes. The cFPI model in mice appears suitable for the study of injury mechanisms, including neuroinflammation, and the development of treatments targeting TAI.

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publication status
published
keywords
Amyloid beta-Protein Precursor, Animals, Astrocytes, Behavior, Animal, Blood-Brain Barrier, Brain Injuries, Cell Count, Diffuse Axonal Injury, Glial Fibrillary Acidic Protein, Immunohistochemistry, Inflammation, Male, Mice, Mice, Inbred C57BL, Neutrophil Infiltration, Treatment Outcome, Vimentin, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Neuroinflammation
volume
10
pages
1 - 19
publisher
BioMed Central
external identifiers
  • scopus:84875688606
ISSN
1742-2094
DOI
10.1186/1742-2094-10-44
language
English
LU publication?
no
id
a1fc6411-6b28-44da-8a1d-b9fd47ac5905
date added to LUP
2016-12-12 15:33:43
date last changed
2018-06-03 04:51:51
@article{a1fc6411-6b28-44da-8a1d-b9fd47ac5905,
  abstract     = {<p>BACKGROUND: Diffuse traumatic axonal injury (TAI), a common consequence of traumatic brain injury, is associated with high morbidity and mortality. Inflammatory processes may play an important role in the pathophysiology of TAI. In the central fluid percussion injury (cFPI) TAI model in mice, the neuroinflammatory and astroglial response and behavioral changes are unknown.</p><p>METHODS: Twenty cFPI-injured and nine sham-injured mice were used, and the neuroinflammatory and astroglial response was evaluated by immunohistochemistry at 1, 3 and 7 days post-injury. The multivariate concentric square field test (MCSF) was used to compare complex behavioral changes in mice subjected to cFPI (n = 16) or sham injury (n = 10). Data was analyzed using non-parametric statistics and principal component analysis (MCSF data).</p><p>RESULTS: At all post-injury time points, β-amyloid precursor protein (β-APP) immunoreactivity revealed widespread bilateral axonal injury and IgG immunostaining showed increased blood-brain barrier permeability. Using vimentin and glial fibrillary acidic protein (GFAP) immunohistochemistry, glial cell reactivity was observed in cortical regions and important white matter tracts peaking at three days post-injury. Only vimentin was increased post-injury in the internal capsule and only GFAP in the thalamus. Compared to sham-injured controls, an increased number of activated microglia (MAC-2), infiltrating neutrophils (GR-1) and T-cells (CD3) appearing one day after TAI (P&lt;0.05 for all cell types) was observed in subcortical white matter. In the MCSF, the behavioral patterns including general activity and exploratory behavior differed between cFPI mice and sham-injured controls.</p><p>CONCLUSIONS: Traumatic axonal injury TAI resulted in marked bilateral astroglial and neuroinflammatory responses and complex behavioral changes. The cFPI model in mice appears suitable for the study of injury mechanisms, including neuroinflammation, and the development of treatments targeting TAI.</p>},
  articleno    = {44},
  author       = {Ekmark-Lewén, Sara and Flygt, Johanna and Kiwanuka, Olivia and Meyerson, Bengt J and Lewén, Anders and Hillered, Lars and Marklund, Niklas},
  issn         = {1742-2094},
  keyword      = {Amyloid beta-Protein Precursor,Animals,Astrocytes,Behavior, Animal,Blood-Brain Barrier,Brain Injuries,Cell Count,Diffuse Axonal Injury,Glial Fibrillary Acidic Protein,Immunohistochemistry,Inflammation,Male,Mice,Mice, Inbred C57BL,Neutrophil Infiltration,Treatment Outcome,Vimentin,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {04},
  pages        = {1--19},
  publisher    = {BioMed Central},
  series       = {Journal of Neuroinflammation},
  title        = {Traumatic axonal injury in the mouse is accompanied by a dynamic inflammatory response, astroglial reactivity and complex behavioral changes},
  url          = {http://dx.doi.org/10.1186/1742-2094-10-44},
  volume       = {10},
  year         = {2013},
}