title: Systemic endotoxin administration results in increased S100B protein blood levels and periventricular brain white matter injury in the preterm fetal sheep.
abstract: OBJECTIVE
  Intrauterine infection is suggested to cause perinatal brain white matter injury. The aim of the present study was to clarify, whether intravenous application of endotoxin results in neuropathological findings and increased blood levels of the S100B protein, which is a consolidated marker of brain injury.
  
  
  METHODS
  Twenty-one fetal sheep were chronically catheterized at a mean gestational age of 107+/-1 days (0.7 of gestation). Three days after surgery fetuses received either 100 (n = 9), 500 (n = 5) or 2500 ng (n = 1) lipopolysaccharide (LPS; E. coli; O127:B8, Sigma-Aldrich) or 2 ml 0.9% saline (n = 6) i.v. S100B protein blood levels were assessed before during and after LPS or placebo administration. Brain damage was evaluated by light microscopy. Selected areas of the periventricular white matter were also examined by electron microscopy.
  
  
  RESULTS
  Histopathological screening revealed no evidence for cortical neuronal cell damage in both groups. However, LPS treatment resulted in inflammatory infiltrates in all animals and cystic lesions in the periventricular brain white matter in two fetuses. On electron micrographs, infiltrate forming cells appeared to be activated microglia. S100B protein blood levels were significantly higher in the LPS group at 1h (p < 0.01) after LPS injection, peaking at 3h (p < 0.001) and returning to baseline between 12 and 72 h.
  
  
  CONCLUSIONS
  Intravenous application of endotoxin caused focal periventricular brain white matter injury, inflammation and an increase in S100B protein release. It is suggested that longitudinal investigations of S100B protein blood levels offer a tool for the early detection of white matter injury.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospitals of Aachen and Cologne, Kerpenerstrasse 62, 50924 Cologne, Germany. yves.garnier@uk-koeln.de
authors.forename: Yves
authors.initials: Y
authors.lastname: Garnier
authors.forename: Richard
authors.initials: R
authors.lastname: Berger
authors.forename: Stephanie
authors.initials: S
authors.lastname: Alm
authors.forename: Monika U
authors.initials: MU
authors.lastname: von Duering
authors.forename: Audrey B C
authors.initials: AB
authors.lastname: Coumans
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Michetti
authors.forename: Matteo
authors.initials: M
authors.lastname: Bruschettini
authors.forename: Mario
authors.initials: M
authors.lastname: Lituania
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Hasaart
authors.forename: Diego
authors.initials: D
authors.lastname: Gazzolo
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008854:Microscopy, Electron; D009414:Nerve Growth Factors / Q000097:blood*; D011247:Pregnancy; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood*; D012756:Sheep
chemical_list: D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins