Development of a guinea pig model of chorioamnionitis and fetal brain injury

Patrick, Lindsay A.; Gaudet, Laura; Farley, Anne E.; Rossiter, John P.; Tomalty, Lewis; Smith, Graeme N.

doi:10.1016/j.ajog.2004.03.016

Cited by 33 publications

(19 citation statements)

References 17 publications

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“…The IL-1␤ and TNF-␣ serum concentrations we attained are similar to those achieved in the guinea pig after instillation of Escherichia coli bacteria into the amniotic cavity to induce chorioamnionitis, causing fetal brain damage (34). In pregnant women, maternal serum levels of IL-1␤ and TNF-␣ are mostly undetectable.…”

Section: Discussionsupporting

confidence: 71%

Intraperitoneal infusion of proinflammatory cytokines does not cause activation of the rat uterus during late gestation

Mitchell¹,

Zavan²,

Wong³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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Increased concentrations of IL-1beta and TNF-alpha have been associated with parturition. However, the role of these cytokines is unknown. Before parturition, the uterus undergoes a process of activation, during which there are significant changes in expression of genes associated with increased uterine contractility, including the receptors for oxytocin (OT) and prostaglandin (PG)F(2alpha) (FP), PGH(2) synthase isoform 2 (PGHS2), the gap junction protein connexin-43 (Cx-43), and the inducible isoform of nitric oxide synthase (iNOS). To determine whether IL-1beta or TNF-alpha was part of the causal mechanism for increased uterine contractions, we placed osmotic pumps infusing IL-1beta or TNF-alpha into the peritoneal cavity of late pregnant rats (gestation day 19) and measured the effects on uterine contractility and on the uterine concentrations of mRNA for the contraction-associated genes 24 h later. Maternal serum concentrations of IL-1beta and TNF-alpha were increased significantly. By day 21, the control animals had significant increases (P < or = 0.05) in mRNA for OT, FP, PGHS2, and Cx-43, a decrease (P < or = 0.05) in iNOS, and an increase (P < or = 0.05) in uterine sensitivity and responsiveness to OT. Infusion of IL-1beta or TNF-alpha had no effect on uterine contractility or on expression of the activation-associated genes. We conclude that intraperitoneal infusion of IL-1beta or TNF-alpha resulting in significantly increased maternal serum cytokine levels does not cause uterine activation. The role of proinflammatory cytokines in the mechanism of parturition remains unclear.

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Section: Discussionsupporting

confidence: 71%

Intraperitoneal infusion of proinflammatory cytokines does not cause activation of the rat uterus during late gestation

Mitchell¹,

Zavan²,

Wong³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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“…Apoptosis has been reported to be a contributing mechanism for cell death in infants with WM injury (29). As previously demonstrated in pregnant rabbits and guinea pigs, E. coli inoculation into the uterine horns or into the cervix resulted in abundant PCD in the WM 2 d later (16,30). Active caspase-3 is initially low in the developing rat brain, but rises rapidly in the prenatal and early postnatal period to a peak and then declines (31).…”

Section: Discussionmentioning

confidence: 75%

Maternal Exposure to LPS Induces Hypomyelination in the Internal Capsule and Programmed Cell Death in the Deep Gray Matter in Newborn Rats

et al. 2006

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Epidemiologic and experimental findings implicate maternal infection in the etiology of injury to brain white matter, which may lead to cerebral palsy in preterm newborns. In the present study, inflammation and brain damage in 1-and 7-d-old rats were investigated after maternal inflammation. Intraperitoneal injection of 300 g/kg of Escherichia coli lipopolysaccharide was administered to pregnant Wistar rats at d 19 and 20 of gestation (LPS group). Control females received a saline injection. Proinflammatory cytokines IL-1␤, tumor necrosis factor-␣, and IL-6 expression in the fetal brain were determined by reverse transcription quantitative polymerase chain reaction. Brain injury was examined in 16-m coronal brain sections by GFAP, MBP, caspase-3 immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Expression of IL-1␤ was significantly increased 3 d after maternal administration (P1). A significant increase in cell death occurred at P1 and P7 in specific brain areas, i.e. in the subventricular striatal zone at P1, and in 1) the periventricular striatum, 2) the periventricular white matter, and 3) the germinative ventricular zone at P7. We also observed typical astrogliosis and strong hypomyelination in the external and internal capsule in the LPS group at P7. These results demonstrate that maternal LPS treatment induces persistent fetal inflammatory reactions associated with significant white matter injury in progeny at P1 and P7. This model should be relevant for the study of the pathophysiological mechanisms involved in cerebral white matter damage in preterm human newborns and in the development of therapeutic strategies. (Pediatr Res 59: [428][429][430][431][432][433] 2006)

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“…These pro-inflammatory mediators damage the brain parenchyma and vasculature without active fetal infection. 3, 4, 5 Elevated pro-inflammatory cytokines also alter the permeability of the fetal blood–brain barrier and important mediators of fetal blood flow, nitric oxide and endothelin-1, rendering the neonate susceptible to further brain injury from relatively minor episodes of hypoxia-ischemia (HI). 6, 7, 8, 9 …”

Section: Introductionmentioning

confidence: 99%

Sex differences in cerebral blood flow following chorioamnionitis in healthy term infants

et al. 2014

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Objective:Sex is an important determinant of neonatal outcomes and may have a significant role in the physiologic response to maternal chorioamnionitis. Our goal was to determine cerebral blood flow (CBF) parameters by sex and subsequent neurodevelopment in healthy term infants exposed to chorioamnionitis.Study Design:CBF by Doppler ultrasound in anterior and middle cerebral (ACA, MCA) and basilar arteries were analyzed for time-averaged maximum velocity (TAMX) and corrected resistive index in 52 term control and chorioamnionitis-exposed infants between 24 and 72 h after birth. Placental pathology confirmed histologic evidence of chorioamnionitis (HC). Bayley Scales of Infant Development-III were administered at 12 months.Result:HC male infants had significantly greater TAMX in the MCA and lower mean MCA and ACA resistance than HC females. Abnormal CBF correlated negatively with neurodevelopmental outcome.Conclusion:CBF is altered in term infants with histologically confirmed chorioamnionitis compared with control infants with sex-specific differences.

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Development of a guinea pig model of chorioamnionitis and fetal brain injury

Cited by 33 publications

References 17 publications

Intraperitoneal infusion of proinflammatory cytokines does not cause activation of the rat uterus during late gestation

Intraperitoneal infusion of proinflammatory cytokines does not cause activation of the rat uterus during late gestation

Maternal Exposure to LPS Induces Hypomyelination in the Internal Capsule and Programmed Cell Death in the Deep Gray Matter in Newborn Rats

Sex differences in cerebral blood flow following chorioamnionitis in healthy term infants

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