Alteration of sphingolipid metabolism as a putative mechanism underlying LPS‐induced BBB disruption

• DOI: 10.1111/jnc.14236
• Publication Date: 2017-10-11T07:42:49Z
• Authors: Rajkumar Vutukuri; Robert Brunkhorst; Roxane‐Isabelle K...; Lena Hansen; Nerea Ferreiros B...; Josef Pfeilschifter; Kavi Devraj; Waltraud Pfeilsch...
• Keywords: Sphingolipid; S1PR1; Vascular permeability; Sphingosine Kinase; Uridine diphosphate

Septic encephalopathy with confusion and agitation occurs early during sepsis contributes to the severity of disease. A decrease in sphingosine-1-phosphate (S1P) blood levels has been shown patients animal models sepsis. The lipid mediator S1P is known be involved endothelial barrier function a context-dependent manner. We utilized lipopolysaccharide (LPS)-injected mice as model for septic first performed tracer permeability assays assess blood-brain (BBB) breakdown vivo. At time points corresponding BBB post LPS injection, we aimed characterize regulation sphingolipid signaling pathway at measured concentrations blood, mouse brain microvessels (MBMVs), tissue. also analyzed expression receptors, transporters, metabolizing enzymes MBMVs Primary microvascular cells (MBMECs) were isolated evaluate effects on transendothelial electrical resistance (TEER) measure vitro. observed relevant after injection all three compartments (blood, MBMVs, tissue) that was accompanied by an increased receptor type 1 sphingosine kinase one hand degrading phosphate phosphatase (LPP1) other hand, well down-regulation 2. Application monolayer primary MBMECs did not alter TEER, but serum from LPS-treated lead compared vehicle-treated mice. profound alterations metabolism point toward therapeutic potential drugs interfering this novel approach detrimental overwhelming immune response Read Editorial Highlight article page 115. Cover Image Issue: doi. 10.1111/jnc.14161.