title: An animal model for chorioamnionitis at term.
abstract: OBJECTIVE
  The purpose of this study was to develop an animal model for intrapartum inflammation at term to investigate the interactions between maternal and fetal inflammatory responses and adverse neurologic outcome.
  
  
  METHODS
  Lipopolysaccharide (160, 320, or 640 μg/kg) was administered intraperitoneally to day 20 term-pregnant Sprague Dawley rat dams 2, 4, and 6 hours before sample collection. Maternal outcomes included dam core temperature and plasma interleukin 6 (IL-6). Fetal outcomes included plasma IL-6, brain IL-6 messenger RNA expression, and brain IL-6 protein expression. Primary cortical cell cultures were prepared to examine neuronal morphologic condition. Neurite counts were obtained with the use of automated Sholl analysis.
  
  
  RESULTS
  Maternal plasma IL-6 levels peaked 2 hours after lipopolysaccharide stimulus and rapidly resolved, except for an observed low level persistence at 6 hours with 640 μg/kg. Fetal plasma and placental IL-6 expression also peaked rapidly but only persisted in placental samples. Fetal brain IL-6 RNA and protein expression was significantly higher than control litters at 6 hours after the exposure to both 320 μg/kg (P ≤ .05) and 640 μg/kg (P ≤ .01). Cortical cells from fetuses that were exposed for 6 hours to maternal systemic inflammation showed reduced neurite number and neurite length (P < .001) with increasing lipopolysaccharide dose.
  
  
  CONCLUSIONS
  Our results demonstrate that fetal brain injury follows isolated systemic maternal inflammation and that fetal brain inflammation lags after maternal stimulus, which creates a potential 4-hour clinical window for therapeutic intervention.
authors.affiliation: Department of Obstetrics and Gynecology, Center for Neural Repair and Rehabilitation, Shriners Hospitals Pediatric Research Center and Department of Obstetrics & Gynecology, Temple University School of Medicine, Philadelphia, PA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Dell'Ovo
authors.affiliation: Department of Obstetrics and Gynecology, Integrated Research Center for Fetal Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Jason
authors.initials: J
authors.lastname: Rosenzweig
authors.affiliation: Department of Obstetrics and Gynecology, Integrated Research Center for Fetal Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Irina
authors.initials: I
authors.lastname: Burd
authors.affiliation: Department of Obstetrics and Gynecology, Center for Neural Repair and Rehabilitation, Shriners Hospitals Pediatric Research Center and Department of Obstetrics & Gynecology, Temple University School of Medicine, Philadelphia, PA.
authors.forename: Nana
authors.initials: N
authors.lastname: Merabova
authors.affiliation: Department of Obstetrics and Gynecology, Center for Neural Repair and Rehabilitation, Shriners Hospitals Pediatric Research Center and Department of Obstetrics & Gynecology, Temple University School of Medicine, Philadelphia, PA.
authors.forename: Nune
authors.initials: N
authors.lastname: Darbinian
authors.affiliation: Department of Obstetrics and Gynecology, Center for Neural Repair and Rehabilitation, Shriners Hospitals Pediatric Research Center and Department of Obstetrics & Gynecology, Temple University School of Medicine, Philadelphia, PA. Electronic address: goetzl@temple.edu.
authors.forename: Laura
authors.initials: L
authors.lastname: Goetzl
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001831:Body Temperature; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D002821:Chorioamnionitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D008070:Lipopolysaccharides; C482199:lipopolysaccharide, E coli O55-B5
keywords: brain injury; cerebral palsy; chorioamnionitis