US EPA

4092826 

Journal Article 

Systemic Endotoxin Administration Results In Increased S100B Protein Blood Levels And Periventricular White Matter Injury In The Preterm Fetal Sheep 

Coumans, AB; Garnier, Y; Gazzolo, D; Alm, S; Von Duering, M; Jensen, A; Berger, R; Hasaart, TH 

2004 

1 

Journal of the Society for Gynecologic Investigation
ISSN: 1071-5576 

DART/TER/4000775 

11 

2 Suppl 

English 

Objective: Intrauterine infection is suggested to cause perinatal white matter injury. The aim of the present study was to clarify, whether application of endotoxin results in neuropathological findings and increased S100B protein blood levels in the preterm ovine fetus. Methods: Twenty fetal sheep were catheterized at a mean gestational age of 107 days (0.7 gestation). Three days later, fetuses received either 100 or 500 nanogram LPS (n=14) or 2 ml saline (n=6). 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 examined by electron microscopy. Results: Histopathological screening revealed no evidence for cortical neuronal cell damage in both LPS and placebo groups. However, LPS resulted in inflammatory infiltrates in all animals and cystic lesions in the periventricular white matter in 2 fetuses. On electron micrographs infiltrate forming cells appeared to be activated microglia. Also, an increased rate of apoptosis and mitosis was found in these regions. S100B protein blood levels were higher in the LPS group at 1 hour (p and lt; 0.01) after LPS injection, peaking at 6 hours (p and lt; 0.001), and returning to baseline between 12 and 72 hours. (Figure: see text). Conclusion: Intravenous application of endotoxin caused sporadic periventricular 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.