Dose-dependent lipopolysaccharide-induced fetal brain injury in the guinea pig.
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.


METHODS
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).


CONCLUSIONS
A threshold of maternal infection/inflammation exists, beyond which demonstrable fetal brain injury may result.
Harnett
Erica L
EL
Department of Anatomy and Cell Biology, Queen's University School of Medicine, Kingston, ON, Canada.
Dickinson
Michelle A
MA
Smith
Graeme N
GN
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006168:Guinea Pigs; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000633:toxicity*; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha