Systemic endotoxin administration results in increased S100B protein blood levels and periventricular brain white matter injury in the preterm fetal sheep.
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.
Garnier
Yves
Y
Department of Obstetrics and Gynecology, University Hospitals of Aachen and Cologne, Kerpenerstrasse 62, 50924 Cologne, Germany. yves.garnier@uk-koeln.de
Berger
Richard
R
Alm
Stephanie
S
von Duering
Monika U
MU
Coumans
Audrey B C
AB
Michetti
Fabrizio
F
Bruschettini
Matteo
M
Lituania
Mario
M
Hasaart
Tom H M
TH
Gazzolo
Diego
D
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
D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins