PMID- 20822466
OWN - NLM
STAT- MEDLINE
DCOM- 20110303
LR  - 20131121
IS  - 1557-9042 (Electronic)
IS  - 0897-7151 (Linking)
VI  - 27
IP  - 11
DP  - 2010 Nov
TI  - Post-traumatic hypoxia exacerbates brain tissue damage: analysis of axonal injury 
      and glial responses.
PG  - 1997-2010
LID - 10.1089/neu.2009.1245 [doi]
AB  - Traumatic brain injury (TBI) resulting in poor neurological outcome is 
      predominantly associated with diffuse brain damage and secondary hypoxic insults. 
      Post-traumatic hypoxia is known to exacerbate primary brain injury; however, the 
      underlying pathological mechanisms require further elucidation. Using a rat model 
      of diffuse traumatic axonal injury (TAI) followed by a post-traumatic hypoxic 
      insult, we characterized axonal pathology, macrophage/microglia accumulation, and 
      astrocyte responses over 14 days. Rats underwent TAI alone, TAI followed by 30 
      min of hypoxia (TAI + Hx), hypoxia alone, or sham-operation (n = 6/group). 
      Systemic hypoxia was induced by ventilating rats with 12% oxygen in nitrogen, 
      resulting in a  approximately  50% reduction in arterial blood oxygen saturation. Brains were 
      assessed for axonal damage, macrophage/microglia accumulation, and astrocyte 
      activation at 1, 7, and 14 days post-treatment. Immunohistochemistry with axonal 
      damage markers (beta-amyloid precursor protein [beta-APP] and neurofilament) showed 
      strong positive staining in TAI + Hx rats, which was most prominent in the corpus 
      callosum (retraction bulbs 69.8 +/- 18.67; swollen axons 14.2 +/- 5.25), and 
      brainstem (retraction bulbs 294 +/- 118.3; swollen axons 50.3 +/- 20.45) at 1 day 
      post-injury. Extensive microglia/macrophage accumulation detected with the CD68 
      antibody was maximal at 14 days post-injury in the corpus callosum (macrophages 
      157.5 +/- 55.48; microglia 72.71 +/- 20.75), and coincided with regions of axonal 
      damage. Astrocytosis assessed with glial fibrillary acidic protein (GFAP) 
      antibody was also abundant in the corpus callosum and maximal at 14 days, with a 
      trend toward an increase in TAI + Hx animals (18.99 +/- 2.45 versus 13.56 +/- 0.81; p 
      = 0.0617). This study demonstrates for the first time that a hypoxic insult 
      following TAI perpetuates axonal pathology and cellular inflammation, which may 
      account for the poor neurological outcomes seen in TBI patients who experience 
      post-traumatic hypoxia.
FAU - Hellewell, Sarah C
AU  - Hellewell SC
AD  - National Trauma Research Institute, The Alfred Hospital, Melbourne, Victoria, 
      Australia.
FAU - Yan, Edwin B
AU  - Yan EB
FAU - Agyapomaa, Doreen A
AU  - Agyapomaa DA
FAU - Bye, Nicole
AU  - Bye N
FAU - Morganti-Kossmann, M Cristina
AU  - Morganti-Kossmann MC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurotrauma
JT  - Journal of neurotrauma
JID - 8811626
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD68 antigen, human)
RN  - 0 (Neurofilament Proteins)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/metabolism
MH  - Blood Gas Analysis
MH  - Blood Pressure/physiology
MH  - Brain/pathology
MH  - Brain Injuries/complications/*pathology
MH  - Corpus Callosum/metabolism
MH  - Diffuse Axonal Injury/*pathology
MH  - Fluorescent Antibody Technique, Indirect
MH  - Gliosis/pathology
MH  - Hypoxia, Brain/etiology/*pathology
MH  - Immunohistochemistry
MH  - Lactic Acid/blood
MH  - Macrophage Activation/physiology
MH  - Male
MH  - Microglia/*pathology
MH  - Neurofilament Proteins/metabolism
MH  - Pyramidal Tracts/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2010/09/09 06:00
MHDA- 2011/03/04 06:00
CRDT- 2010/09/09 06:00
PHST- 2010/09/09 06:00 [entrez]
PHST- 2010/09/09 06:00 [pubmed]
PHST- 2011/03/04 06:00 [medline]
AID - 10.1089/neu.2009.1245 [doi]
PST - ppublish
SO  - J Neurotrauma. 2010 Nov;27(11):1997-2010. doi: 10.1089/neu.2009.1245.