Chorioamnionitis induced by intraamniotic lipopolysaccharide resulted in an interval-dependent increase in central nervous system injury in the fetal sheep

Gavilanes, Antonio W. D.; Strackx, Eveline; Kramer, Boris W.; Gantert, Markus; Hove, Daniël L.A. van den; Steinbusch, H.W.M.; Garnier, Yves; Cornips, Erwin M. J.; Steinbusch, Harry; Zimmermann, Luc J. I.; Vles, Johan S.H.

doi:10.1016/j.ajog.2008.12.003

Cited by 51 publications

(65 citation statements)

References 47 publications

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“…*p Ͻ 0.05; **p Ͻ 0.01; and p Ͻ 0.001 significant difference from saline-injected group. ery (28). Comparable effects were found in the gut, where endotoxin-induced chorioamnionitis did not induce an early inflammatory response.…”

Section: Discussionmentioning

confidence: 95%

“…In previous studies, we already investigated the inflammatory response to chorioamnionitis in lungs, brain, and gut using the same fetal sheep model (10,28). We have shown that endotoxin evoked a pulmonary inflammatory response 2 d after injections (10), which is not mediated by cortisol (29) and induced oxidative stress in the fetal lung (27,30).…”

Section: Discussionmentioning

confidence: 99%

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Chorioamnionitis Induced Hepatic Inflammation and Disturbed Lipid Metabolism in Fetal Sheep

et al. 2010

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Chorioamnionitis frequently induces a fetal inflammatory response syndrome (FIRS), characterized by an elevation of proinflammatory mediators and systemic inflammation. Although there is increasing evidence that inflammation and lipid metabolism influence each other, the effects of chorioamnionitis-induced FIRS on fetal lipid homeostasis are currently not known. Accordingly, we hypothesize that chorioamnionitis induces an inflammatory response in the fetal liver, consequently leading to metabolic disturbances. Chorioamnionitis was induced by intra-amniotic injection of 10 mg endotoxin (control) for 2 d or 2 wk before delivery. Saline injections were given to controls. The effect of chorioamnionitis on hepatic inflammation and metabolic parameters was analyzed in ovine fetuses at the GA of 125 d (normal GA ϭ 150 d). We found that 2 d after the endotoxin injections, inflammatory markers were significantly higher compared with controls. In addition, lipid and glucose metabolism were disturbed in response to endotoxin. Moreover, the antioxidant state capacity was reduced, and hepatic damage was apparent. Two weeks after the endotoxin injections, the fetal livers were still inflamed and had higher glucose concentrations in the blood. In addition, the levels of markers for hepatic damage (alanine aminotransferase and aspartate aminotransferase) were increased. In conclusion, chorioamnionitis induces liver inflammation leading to metabolic disturbances in the fetus. (Pediatr Res 68: 466-472, 2010)

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Chorioamnionitis Induced Hepatic Inflammation and Disturbed Lipid Metabolism in Fetal Sheep

et al. 2010

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“…17 We showed global central nervous system compromise after chorioamnionitis induced by the intra-amniotic administration of lipopolysaccharide (LPS) in the fetal sheep. 18 Chorioamnionitis induced microglial activation, astrogliosis and apoptotic cell death and differentially affected the whole ovine central nervous system. Regional responses varied as a function of its maturational stage; for example, brain and cerebellar, but not spinal premyelinating oligodendrocytes, were found to be vulnerable at the gestational age of 125 days (term being 150 days).…”

Section: Multiorgan Overviewmentioning

confidence: 99%

“…Regional responses varied as a function of its maturational stage; for example, brain and cerebellar, but not spinal premyelinating oligodendrocytes, were found to be vulnerable at the gestational age of 125 days (term being 150 days). 18 In addition, Garnier et al 19 showed microglial activation in the periventricular and subcortical white matter and increased S100B protein blood levels in a model of intravenous fetal LPS administration at a gestational age of 107 days.…”

Section: Multiorgan Overviewmentioning

confidence: 99%

“…20 The activated microglia in the diffuse white matter lead to the apoptotic death of the developing oligodendrocytes by two mechanisms. First, in addition to the systemic upregulated proinflammatory cytokines, the diffuse microglial production of proinflammatory cytokines, for example, tumor necrosis factor-a (TNF-a), IL-1, IL-6 and interferon-g, affects mainly the cerebral fetal white matter oligodendrocytes, 18 and secondarily induces neuronal loss and impaired neuronal guidance, 21 with high levels of proinflammatory cytokines. 22 Although low cytokine levels are crucial for the maturation and differentiation of oligodendrocyte precursors into myelinating mature oligodendrocytes, high levels of proinflammatory cytokines, as found in inflamed fetal brains, inhibit this process.…”

Section: Multiorgan Overviewmentioning

confidence: 99%

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Chorioamnionitis: a multiorgan disease of the fetus?

et al. 2010

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The bacterial infection of chorion and amnion is a common finding in premature delivery and is referred to as chorioamnionitis. As the mother rarely shows symptoms of a systemic inflammation, the course of chorioamnionitis is frequently asymptomatic and chronic. In contrast, the fetal inflammatory response syndrome represents a separate phenomenon, including umbilical inflammation and increased serum levels of proinflammatory cytokines in the fetus. Ascending maternal infections frequently lead to systemic fetal inflammatory reaction. Clinical studies have shown that antenatal exposure to inflammation puts the extremely immature neonates at a high risk for worsening pulmonary, neurological and other organ development. Interestingly, the presence of chorioamnionitis is associated with a lower rate of neonatal mortality in extremely immature newborns. In the following review, the pathogeneses of inflammation-associated perinatal morbidity are outlined. The concept of fetal multiorganic disease during intrauterine infection is introduced and discussed.

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