• Kristo Erikson, Hannu Tuominen, Merja Vakkala, Janne Henrik Liisanantti, Tuomo Karttunen, Hannu Syrjälä, and Tero Ilmari Ala-Kokko.
• Division of Intensive Care Medicine, Department of Anesthesiology, Research Group of Surgery, Anesthesiology and Intensive Care Medicine, Oulu University Hospital, Medical Research Center Oulu, University of Oulu, Oulu, Finland. kristo.erikson@regionaalhaigla.ee.
• Crit Care. 2020 Jun 29; 24 (1): 385.

BackgroundNeuroinflammation often develops in sepsis along with increasing permeability of the blood-brain barrier (BBB), which leads to septic encephalopathy. The barrier is formed by tight junction structures between the cerebral endothelial cells. We investigated the expression of tight junction proteins related to endothelial permeability in brain autopsy specimens in critically ill patients deceased with sepsis and analyzed the relationship of BBB damage with measures of systemic inflammation and systemic organ dysfunction.MethodsThe case series included all (385) adult patients deceased due to sepsis in the years 2007-2015 with available brain specimens taken at autopsy. Specimens were categorized according to anatomical location (cerebrum, cerebellum). The immunohistochemical stainings were performed for occludin, ZO-1, and claudin. Patients were categorized as having BBB damage if there was no expression of occludin in the endothelium of cerebral microvessels.ResultsBrain tissue samples were available in 47 autopsies, of which 38% (18/47) had no expression of occludin in the endothelium of cerebral microvessels, 34% (16/47) developed multiple organ failure before death, and 74.5% (35/47) had septic shock. The deceased with BBB damage had higher maximum SOFA scores (16 vs. 14, p = 0.04) and more often had procalcitonin levels above 10 μg/L (56% vs. 28%, p = 0.045) during their ICU stay. BBB damage in the cerebellum was more common in cases with C-reactive protein (CRP) above 100 mg/L as compared with CRP less than 100 (69% vs. 25%, p = 0.025).ConclusionsIn fatal sepsis, damaged BBB defined as a loss of cerebral endothelial expression of occludin is related with severe organ dysfunction and systemic inflammation.

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