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. 2022 Mar 31;27(6):2659–2673. doi: 10.1038/s41380-022-01511-z

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© The Author(s) 2022

Open Access This 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/..

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Fig. 2 — A Passive diffusion across endothelial cells by a limited number of small molecules (blue). B Paracellular transport of limited water-soluble agents (pink) between endothelial cells, through tight junction proteins. C Active efflux transporters (yellow) mostly eliminate drugs and substanes from the brain include many ATP binding cassette (ABC) transporters (purple) which are P-glycoprotein (Pgp), multidrug resistance proteins (MRPs), and breast cancer resistance protein (BCRP). D Carrier-mediated transport can be in either direction depending on the transporter and can be clatherin-dependent endocytosis. Major transporters include the glucose carrier (GLUT1), the L-type amino acid transporter 1 and 2 (LAT1/2), cationic amino acid transporter 1 and 3 (CAT1/3), the monocarboxylic acid carrier (MCT1/8), the organic anion transporting polypeptide 1c1 (OATP1C1), the fatty acid transport protein 1 and 4 (FATP1/4), the sodium-independent concentrative nucleoside transporter-2 (CNT2), the organic anion transporter 3 (OAT3), organic anion transporter poypeptide 1a4 and 2b1 (OATP1A4 and OATP2B1), and the organic cation transporter 2 (OCTN2). E Receptor-mediated transport relies on the interaction between ligands (green) and receptors to transport larger molecules through the cells. These receptors include the transferrin receptor (TfR), insulin receptor (IR), leptin receptor (LEP-R), lipoprotein receptor 1 and 2 (LRP1/2), and the receptor for advanced glycation end products (RAGE). F Absorptive-mediated transport is caveolin-mediated endocytosis and relies on the interaction between the ligand (orange) and the glycocalyx on the endothelial cells. G Ion transporters (turquoise) regulate the ions between the barrier and includes sodium pumps, calcium transporters, and potassium channels.