Synergistic white matter protection with acute-on-chronic endotoxin and subsequent asphyxia in preterm fetal sheep

Journal of Neuroinflammation

Laura Bennet²  Alistair J Gunn²  Mhoyra Fraser¹  Lindsea C Booth²  Christopher A Lear²  Joanne O Davidson²  Sam Mathai²  Lotte G van den Heuij² 

[1]The Liggins Institute, University of Auckland, Park Road, Grafton, Auckland 1023, New Zealand

[2]Department of Physiology, University of Auckland, Park Road, Grafton, Auckland 1023, New Zealand

关键词: Preconditioning;    Postconditioning;    Lipopolysaccharide;    Inflammation;    Fetus;    Asphyxia;   

Others  :  804221
DOI  :  10.1186/1742-2094-11-89

 received in 2014-03-15, accepted in 2014-05-01,  发布年份 2014

【 摘 要 】

Background

Perinatal asphyxia and exposure to intrauterine infection are associated with impaired neurodevelopment in preterm infants. Acute exposure to non-injurious infection and/or inflammation can either protect or sensitize the brain to subsequent hypoxia-ischemia. However, the effects of subacute infection and/or inflammation are unclear. In this study we tested the hypothesis that acute-on-chronic exposure to lipopolysaccharide (LPS) would exacerbate white matter injury after subsequent asphyxia in preterm fetal sheep.

Methods

Fetal sheep at 0.7 gestational age received a continuous LPS infusion at 100 ng/kg for 24 hours, then 250 ng/kg/24 hours for 96 hours, plus 1 μg boluses of LPS at 48, 72, and 96 hours or the same volume of saline. Four hours after the last bolus, complete umbilical cord occlusion or sham occlusion was induced for 15 minutes. Sheep were sacrificed 10 days after the start of infusions.

Results

LPS exposure was associated with induction of microglia and astrocytes and loss of total and immature and mature oligodendrocytes (n = 9) compared to sham controls (n = 9). Umbilical cord occlusion with saline infusions was associated with induction of microglia, astrogliosis, and loss of immature and mature oligodendrocytes (n = 9). LPS exposure before asphyxia (n = 8) was associated with significantly reduced microglial activation and astrogliosis and improved numbers of immature and mature oligodendrocytes compared to either LPS exposure or asphyxia alone.

Conclusions

Contrary to our initial hypothesis, the combination of acute-on-chronic LPS with subsequent asphyxia reduced neuroinflammation and white matter injury compared with either intervention alone.

【 授权许可】

   
2014 van den Heuij et al.; licensee BioMed Central Ltd.

【 图 表 】

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