Combined in utero hypoxia-ischemia and lipopolysaccharide administration in rats induces chorioamnionitis and a fetal inflammatory response syndrome.
Document Type
Article
Publication Date
12-1-2015
Abstract
INTRODUCTION: Preterm birth is a major cause of infant morbidity and long-term disability, and is associated with numerous central nervous system (CNS) deficits. Infants exposed to intrauterine inflammation, specifically chorioamnionitis, are at risk for very early preterm birth and neurological complications including cerebral palsy, epilepsy, and behavioral and cognitive deficits. However, placenta-brain axis abnormalities and their relationship to subsequent permanent CNS injury remain poorly defined.
METHODS: Intrauterine injury was induced in rats on embryonic day 18 (E18) by transient systemic hypoxia-ischemia (TSHI) and intra-amniotic lipopolysaccharide (LPS) injection. Placenta, brain and serum were collected from E19 to postnatal day 0 (P0). Histology, TUNEL staining, western blot and multiplex immunoassays were used to quantify placental and brain abnormalities, and fetal serum cytokine levels.
RESULTS: Prenatal TSHI + LPS caused acute and subacute placental injury hallmarked by inflammatory infiltrate, edema, hemorrhage and cell death along with placental increases in IL-1β and TNFα. TSHI + LPS increased a diverse array of circulating inflammatory proteins including IL-1β, TNFα, IL-6, IL-10, IL-4, IFNγ and CXCL1, both immediately after TSHI + LPS and in live born pups. CNS inflammation was characterized by increased CXCL1.
DISCUSSION: Prenatal TSHI + LPS in rats induces placental injury and inflammation histologically consistent with chorioamnionitis, concomitant with elevated serum and CNS pro-inflammatory cytokines. This model accurately recapitulates key pathophysiological processes observed in extremely preterm infants including placental, fetal, and CNS inflammation. Further investigation into the mechanism of CNS injury following chorioamnionitis and the placental-brain axis will guide the use of future interventions.
Publication Title
Placenta
ISSN
1532-3102
Volume
36
Issue
12
First Page
1378
Last Page
1384
Recommended Citation
Maxwell, Jessie R; Jesse L Denson; Nancy E Joste; Shenandoah Robinson; and Lauren L Jantzie.
"Combined in utero hypoxia-ischemia and lipopolysaccharide administration in rats induces chorioamnionitis and a fetal inflammatory response syndrome.."
Placenta
