Degree
Master of Science
Program
Physiology
Supervisor
Dr. Douglas Fraser
Abstract
Sepsis-associated encephalopathy (SAE) is an independent predictor of mortality in severe sepsis patients. Mechanisms of SAE are poorly characterized. Pro-inflammatory mediators are up-regulated in blood plasma of severe sepsis patients and may lead to activation/dysfunction of cerebrovascular endothelial cells (CMEC) of the blood-brain barrier (BBB) – potentially contributing to brain dysfunction. The objective of the present study was to determine the effects/mechanisms of both human severe sepsis blood plasma (hSSP; 20% v/v) and a mixture of 8 cytokines/chemokines that mimicked physiological concentrations of cytokines/chemokines in hSSP (cytomix; SSCM) on human-derived CMEC (hCMEC/D3) activation/dysfunction
in vitro. hSSP-stimulation up-regulated hCMEC/D3 pro-adhesive phenotype as evidenced by polymorphonuclear leukocyte (PMN; neutrophils) adhesion under conditions of flow. In contrast, up-regulation of the PMN pro-adhesive phenotype was observed following stimulation with the severe sepsis cytomix. These findings suggest that PMN-endothelial interactions may play a key role in dysfunction of cerebrovascular endothelium during severe sepsis.
Recommended Citation
Blom, Christopher J., "Human Cerebrovascular Endothelial Cell Responses in Severe Sepsis" (2012). Electronic Thesis and Dissertation Repository. 733.
https://ir.lib.uwo.ca/etd/733