Increased maternal/fetal blood S100B levels following systemic endotoxin administration and periventricular white matter injury in preterm fetal sheep.
OBJECTIVE
Intrauterine infection is suggested to cause perinatal brain white matter injury. In the current study, we evaluated whether S100B, a brain damage marker, may be also assessed in maternal bloodstream after white matter injury induced by fetal intravenous application of lypopolisaccharide (LPS) endotoxin.


METHODS
Fourteen fetal sheeps were chronically catheterized at a mean gestational age of 107 days. Three days after surgery, fetuses (n = 7) received 500 ng of LPS or 2 mL 0.9% saline (n = 7) intravenously (IV). Lypopolisaccharide and placebo groups were monitored by continuous hemodynamic data recordings and at 6 predetermined time points (control value; 3, 6, 24, 48, and 72 hours after LPS/placebo administration) blood was drawn for laboratory parameters and S100B assessment. Brain damage was evaluated by light microscopy after Klüver-Barrera staining. Selected areas of the periventricular white matter were also examined by electron microscopy.


RESULTS
White matter injury was detected in all LPS-treated fetuses, whereas no abnormalities were seen in control animals or in LPS-treated mothers. Maternal and fetal S100B protein levels were significantly higher in the LPS group than in the control group at all monitoring time points (P < .001). The highest fetal-maternal S100B levels were observed at 3-hour time-point (P < .001).


CONCLUSIONS
We found that S100B protein is increased in the maternal district in presence of fetal periventricular brain white matter injury induced by endotoxin. The present data offer additional support for S100B assessment in the maternal circulation in pregnancies complicated by intrauterine infection at risk of white matter injury.
Garnier
Yves
Y
Department of Obstetrics and Gynecology, University Hospitals of Aachen and Cologne, Germany.
Frigiola
Alessandro
A
Li Volti
Giovanni
G
Florio
Pasquale
P
Frulio
Rosanna
R
Berger
Richard
R
Alm
Stephanie
S
von Duering
Monika U
MU
Coumans
Audrey B C
AB
Reis
Fernando M
FM
Petraglia
Felice
F
Hasaart
Tom H M
TH
Abella
Raoul
R
Mufeed
Hala
H
Gazzolo
Diego
D
D000136:Acid-Base Equilibrium; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D001921:Brain / Q000648:ultrastructure; D001930:Brain Injuries / Q000097:blood* / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D002245:Carbon Dioxide / Q000097:blood; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000097:blood* / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005865:Gestational Age; D006340:Heart Rate, Fetal; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors / Q000097:blood*; D010100:Oxygen / Q000097:blood; D011247:Pregnancy; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood*; D012756:Sheep; D013997:Time Factors; D015854:Up-Regulation
D015415:Biomarkers; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D002245:Carbon Dioxide; D010100:Oxygen