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Updated: Jul 13, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Dose-dependent lipopolysaccharide-induced fetal brain injury in the guinea pig
Erica L Harnett1, Michelle A Dickinson, Graeme N Smith
1Department of Anatomy and Cell Biology, Queen's University School of Medicine, Kingston, ON, Canada.
Objective:
This study determined whether a lipopolysaccharide (LPS) dose-dependent increase in fetal brain injury occurs to further characterize the relationship between maternal inflammation and fetal brain injury.
Study Design:
Pregnant guinea pigs (n = 59) at 70% gestation were injected intraperitoneally with 1, 5, 25, 50, 100, 200, or 300 microg LPS per kilogram of maternal body weight or an equivalent volume of vehicle. Animals were killed 7 days later. Maternal serum and amniotic fluid samples were assayed for proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 using enzyme-linked immunosorbent assay kits. Fetal brains (n = 72) were stained for evidence of cell death with NeuroTACS stain.
Results:
Seven days after LPS injections, cytokine concentrations in maternal serum and amniotic fluid were not different (P > .05) from controls. Levels of cell death in all brain regions examined were highest following the maternal administration of 300 mug/kg LPS (P < .05). The dose effect was brain region-dependent (P < .05).
Conclusion:
A threshold of maternal infection/inflammation exists, beyond which demonstrable fetal brain injury may result.
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