Lipopolysaccharide enters the rat brain by a lipoprotein-mediated transport mechanism in physiological conditions

Abstract

Physiologically, lipopolysaccharide (LPS) is present in the bloodstream and can be bound to several proteins for its transport (i.e.) LPS binding protein (LBP) and plasma lipoproteins). LPS receptors CD14 and TLR-4 are constitutively expressed in the Central Nervous System (CNS). To our knowledge, LPS infiltration in CNS has not been clearly demonstrated. A naturalistic experiment with healthy rats was performed to investigate whether LPS is present with its receptors in brain. Immunofluorescences showed that lipid A and core LPS were present in circumventricular organs, choroid plexus, meningeal cells, astrocytes, tanycytes and endothelial cells. Co-localization of LPS regions with CD14/TLR-4 was found. The role of lipoprotein receptors (SR-BI, ApoER2 and LDLr) in the brain as targets for a LPS transport mechanism by plasma apolipoproteins (i.e. ApoAI) was studied. Co-localization of LPS regions with these lipoproteins markers was observed. Our results suggest that LPS infiltrates in the brain in physiological conditions, possibly, through a lipoprotein transport mechanism, and it is bound to its receptors in blood-brain interfaces.