1. Figure 2 Key transport properties of the capillary endothelium
Figure 2 | Key transport properties of the capillary endothelium. a | Tight junctions (TJ), adherens junctions (AJ) and junctional adhesion molecules (JAMs) prevent free paracellular exchanges of solutes. Lack of pinocytosis and bulk flow transcytosis contribute to the endothelial barrier function. b | O2 and CO2 cross the blood–brain barrier (BBB) by simple diffusion, as do small lipophilic molecules such as ethanol. c | Solutes (metabolites, nutrients, vitamins, nucleotides and other substrates) cross the BBB by carrier-mediated transport (CMT) according to substrate specificity and concentration gradient. d | Receptor-mediated transcytosis (RMT) transports peptides and proteins. e | Sodium-dependent lysophosphatidylcholine symporter 1 (NLS1) transports ω3 essential fatty acids into the brain. f | Ion concentrations are regulated by the abluminal sodium pump (Na+/K+-ATPase), the luminal Na+/H+ exchanger, Cl–/HCO3– exchanger, luminal Na+/K+/Cl– cotransporter and Na+/Ca2+ exchanger. Water is transported via aquaporin (AQP) receptors: AQP1 on endothelial cells and AQP4 on astrocyte end-feet. g | ATP-binding cassette (ABC) active efflux transporters limit entry of drugs, xenobiotic products and drug conjugates. h | Neurotoxic substances are cleared by phosphatidylinositol-binding clathrin assembly protein (PICALM)-mediated transcytosis and by LDL receptor-related protein 1 (LRP1), which removes toxic amyloid‑β (Aβ) species linked to Alzheimer disease (AD). However, levels of receptor for advanced glycosylation end products (RAGE) are increased in AD, which promotes increased re‑entry of circulating Aβ, thereby increasing brain Aβ levels. The CMT transporters, excitatory amino acid transporter 1 (EAAT1) and excitatory amino acid transporter 2 (EAAT2) clear neurotoxic glutamate and aspartate. i | Solutes diffusing across the brain extracellular spaces (ECS) (dotted arrows) are cleared via transvascular transport (as in parts c–e,g–i) and by perivascular ISF flow within the arterial wall in the reverse direction to blood flow, eventually reaching the CSF-filled subarachnoid space and draining into meningeal lymphatic vessels and cervical lymph nodes. ApoE, apolipoprotein E; ApoJ, apolipoprotein J.
Sweeney, M. D. et al. (2018) Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Nat. Rev. Neurol. doi: /nrneurol