PMID- 23557178
OWN - NLM
STAT- MEDLINE
DCOM- 20131105
LR  - 20240321
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 10
DP  - 2013 Apr 4
TI  - Traumatic axonal injury in the mouse is accompanied by a dynamic inflammatory 
      response, astroglial reactivity and complex behavioral changes.
PG  - 44
LID - 10.1186/1742-2094-10-44 [doi]
AB  - 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, beta-amyloid precursor protein (beta-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.
FAU - Ekmark-Lewen, Sara
AU  - Ekmark-Lewen S
AD  - Department of Neuroscience, Division of Neurosurgery, Uppsala University, Uppsala 
      751 85, Sweden.
FAU - Flygt, Johanna
AU  - Flygt J
FAU - Kiwanuka, Olivia
AU  - Kiwanuka O
FAU - Meyerson, Bengt J
AU  - Meyerson BJ
FAU - Lewen, Anders
AU  - Lewen A
FAU - Hillered, Lars
AU  - Hillered L
FAU - Marklund, Niklas
AU  - Marklund N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130404
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Vimentin)
SB  - IM
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Astrocytes/*pathology
MH  - Behavior, Animal/*physiology
MH  - Blood-Brain Barrier/physiology
MH  - Brain Injuries/pathology/psychology
MH  - Cell Count
MH  - Diffuse Axonal Injury/*pathology/*psychology
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Immunohistochemistry
MH  - Inflammation/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neutrophil Infiltration/physiology
MH  - Treatment Outcome
MH  - Vimentin/metabolism
PMC - PMC3651302
EDAT- 2013/04/06 06:00
MHDA- 2013/11/06 06:00
PMCR- 2013/04/04
CRDT- 2013/04/06 06:00
PHST- 2012/09/27 00:00 [received]
PHST- 2013/03/07 00:00 [accepted]
PHST- 2013/04/06 06:00 [entrez]
PHST- 2013/04/06 06:00 [pubmed]
PHST- 2013/11/06 06:00 [medline]
PHST- 2013/04/04 00:00 [pmc-release]
AID - 1742-2094-10-44 [pii]
AID - 10.1186/1742-2094-10-44 [doi]
PST - epublish
SO  - J Neuroinflammation. 2013 Apr 4;10:44. doi: 10.1186/1742-2094-10-44.