Endotoxemia rocks sphingolipid metabolism at the blood-brain barrier: An Editorial Highlight for 'Alteration of sphingolipid metabolism as a putative mechanism underlying LPS-induced BBB disruption' on page 172.

In this issue of the Journal of Neurochemistry, Vutukuri et al. evaluate the impact of endotoxemia-induced encephalopathy on the sphingosine-1-phosphate (S1P) signaling pathway at the blood-brain barrier (BBB). Four hours after intraperitoneal administration of lipopolysaccharides (LPS, 4 mg/kg) to mice, they first demonstrate BBB dysfunction and then evaluate changes in sphingolipid metabolites in serum, isolated brain microvessels (MBMV), and whole brain. In parallel, they investigate the fate of indicated S1P generating and metabolizing enzymes and S1P receptors in brain and MBMV. S1P levels decreased in serum and brain and a similar tendency was observed in MBMV. Sphk2 expression was strongly reduced in MBMV together with an up-regulation of lipid phosphate and S1P phosphatases, resulting in a net decrease in S1P levels despite a compensatory increase in Sphk1 expression. The implications of disturbed sphingolipid metabolism for the pathogenesis of septic encephalopathy will depend on the net impact of these changes on S1P receptor signaling at the BBB and the importance of the S1P pathway in regulating vascular homeostasis in this context.