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. 2021 Dec 7;10:49. doi: 10.1186/s40035-021-00273-y

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — Mechanisms of lipopolysaccharide (LPS) penetration to the central nervous system. LPS produced in the peripheral system penetrates the BBB and enters the brain. ① LBP is a soluble acute-phase protein that binds to bacterial LPS to elicit immune responses. LBP facilitates LPS penetration of the BBB through various receptors, such as Scavenger reception class B type 1 (SR-B1) and apolipoprotein E receptor 2 (ApoER2). ② LPS is transported to BBB by peripheral immune cells. ③ LPS enters the brain via damaged BBB caused by high concentrations of LPS and LPS-induced pro-inflammatory cytokines. ④ LPS is directly recognized by the cell surface pattern recognition receptor CD14/TLR 14 complex, resulting in penetration to the BBB. ⑤ LPS is transported into the brain through gram-negative bacteria transporters, such as OMV. CD14: Cluster of differentiation 14; CNS: Central nervous system; LBP: Lipopolysaccharide-binding protein; OMV: Outer membrane vesicle; PNS: Peripheral nervous system; TLR4: Toll-like receptor 4; VCAM1: Vascular cell adhesion molecules-1