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The Brain Is a Source of S100B Increase During Endotoxemia in the Pig

Miklos Lipcsey, MD, PhD^*, Matts Olovsson, MD, PhD, Erik Larsson, MD, PhD, Roland Einarsson, PhD, Goran A. Qadhr, MD^||, Jan Sjölin, MD, PhD^¶, and Anders Larsson, MD, PhD^#

From the *Section of Anesthesiology & Intensive Care, Department of Surgical Sciences, Departments of Women's and Children's Health and Genetics and Pathology, Uppsala University, Uppsala; Fujirebio Diagnostics AB, Gothenburg; ||Section of Radiology, Department of Oncology, Radiology and Clinical Immunology, ¶Section of Infectious diseases, Department of Medical Sciences, and #Section of Clinical Chemistry, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Address correspondence and reprint requests to Miklos Lipcsey, MD, PhD, Section of Anesthesiology & Intensive Care, Department of Surgical Sciences, Uppsala University, SE-751 85 Uppsala, Sweden. Address e-mail to mlipcsey{at}eml.cc.

Abstract

Background: Cerebral dysfunction frequently complicates septic shock. A marker of cerebral dysfunction could be of significant value in managing sedated septic patients. Plasma S100 (S100B) proteins increase in sepsis. S100B is present not only in the brain but also in other tissues. The source of this protein has not been investigated in sepsis. Our aim in this study was to determine whether the brain is an important source of S100B in an experimental sepsis model.

Methods: Twenty-seven pigs were anesthetized and randomized to either infusion of endotoxin at the rate of 1 µg · kg^–1 · h^–1 (n = 19) or saline (n = 8). Catheters were inserted into a cervical artery and the superior sagittal sinus. Blood samples were collected from both sites and physiologic data were registered before the start of the endotoxin infusion and hourly during the experiment. After 6 h, the animals were killed and brain tissue samples were taken from the left hemisphere. S100B in plasma was measured by enzyme-linked immunosorbent assay. Brain tissue samples were stained with biotinylated S100B antibodies.

Results: In the endotoxemic animals, the arterial S100B concentration increased to 442 ± 33 and 421 ± 24 ng/L at 1 and 2 h, respectively, vs 306 ± 28 and 261 ± 25 ng/L in controls (P = 0.018 and 0.00053, respectively). Mean superior sagittal sinus S100B concentrations were higher than mean arterial concentrations at all time points in the endotoxemic animals; however, significance was only reached at 2 h (P = 0.033). The focal glial S100B expression was more intense in the endotoxemic pigs than in controls (P = 0.0047).

Conclusions: Our results support the hypothesis that the brain is an important source of S100B in endotoxemia even though there may be other sources. These findings make S100B a candidate as a marker of cerebral dysfunction in septic shock.