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Increased Maternal/Fetal Blood S100B Levels Following Systemic Endotoxin Administration and Periventricular White Matter Injury in Preterm Fetal Sheep

Department of Obstetrics and Gynecology, University Hospitals of Aachen and Cologne, Germany, Research Institute Growth and Development, GROW, University Hospital Maastricht, The Netherlands

Alessandro Frigiola, MD

Perinatal Research Laboratory, Department of Cardiac Surgery, S. Donato Milanese University Hospital, San Donato Milanese, Italy

Giovanni Li Volti, PhD

Department Biochemistry, University of Catania, Catania, Italy

Pasquale Florio, PhD

Departments of Pediatrics, Obstetrics & Reproductive Medicine, Section of Obstetrics and Gynecology, University of Siena, Siena, Italy

Rosanna Frulio, MD

Department of Pediatrics and Neuroscience, Giannina Gaslini Children's University Hospital, Genoa

Richard Berger, MD

Department of Obstetrics and Gynecology, University of Bochum, Germany

Stephanie Alm, MD

Department of Obstetrics and Gynecology, University Hospitals of Aachen and Cologne, Germany

Monika U. von Duering, MD

Institute of Neuroanatomy, University of Bochum, Germany

Audrey B.C. Coumans, MD

Research Institute Growth and Development, GROW, University Hospital Maastricht, The Netherlands, University Hospital Maastricht, Department of Obstetrics and Gynecology, Netherlands

Fernando M. Reis, PhD

Departments of Pediatrics, Obstetrics & Reproductive Medicine, Section of Obstetrics and Gynecology, University of Siena, Siena, Italy

Felice Petraglia, MD

Departments of Pediatrics, Obstetrics & Reproductive Medicine, Section of Obstetrics and Gynecology, University of Siena, Siena, Italy

Tom H.M. Hasaart, MD

Research Institute Growth and Development, GROW, University Hospital Maastricht, The Netherlands, University Hospital Maastricht, Department of Obstetrics and Gynecology, Netherlands, Department of Neonatology, Cairo University, Cairo, Egypt

Raoul Abella, MD

Perinatal Research Laboratory, Department of Cardiac Surgery, S. Donato Milanese University Hospital, San Donato Milanese, Italy

Hala Mufeed, MD

Diego Gazzolo, PhD

Department of Pediatrics and Neuroscience, Giannina Gaslini Children's University Hospital, Genoa, Department of Maternal, Fetal and Neonatal Medicine, G. Garibaldi Hospital, Catania, Italy, dgazzolo{at}hotmail.com

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.

Key Words: Fetal brain damage • perinatal infection • preterm delivery • white matter injury • LPS • endotoxin.

This version was published on August 1, 2009

Reproductive Sciences, Vol. 16, No. 8, 758-766 (2009)
DOI: 10.1177/1933719109335801


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