Fig. 1

Illustration of key borders between the blood and brain and between the blood and cerebrospinal fluid (CSF). Blood–brain border (neurovascular unit): cerebral endothelial cells in the parenchyma of the brain contain tight junctions and express numerous transporters and receptors that regulate the transfer of substances between the blood and brain (upper right), as shown by the following examples: Efflux transporters (e.g. P-glycoprotein, ABCB1; breast cancer resistance protein, ABCG2) prevent brain entry of many circulating endogenous substances as well as xenobiotics (drugs). The glucose transporter 1 (GLUT1, SLC2A1) and transferrin receptor (TfR, CD71) mediate brain homeostasis of glucose and iron, respectively, through the uptake of circulating glucose and iron-bound transferrin. The major facilitator superfamily domain containing 2a (MFSD2A) is a fatty acid transporter that is specifically expressed in CNS endothelial cells; MFSD2A also serves an important role in inhibiting clathrin-independent caveolae-mediated transcytosis [37, 38]). Outer blood-CSF border (meninges): outer arachnoid epithelial border cells contain tight junctions and express numerous transporters and receptors (not shown) that potentially assist in the regulated transfer of substances between the blood and extraventricular CSF (bottom right). Inner blood-CSF border (choroid plexus): choroid plexus epithelial cells contain tight junctions and express numerous channels, transporters, receptors and enzymes (not shown) that regulate the composition of CSF (bottom left). As examples, a finely tuned interplay between apically and basolaterally located inorganic anion transporters and channels is responsible for CSF production [39]. Transporters of the ABCC, SLC0, SLC21 families control CSF concentration of potentially deleterious endo and xenobiotics [4], helped by efficient enzymatic detoxification mechanisms [40]. The choroidal transport or secretion of growth factors, hormones and proteins into the brain participates in processes essential for brain development and homeostatic balance [33, 41]. Schematics based in part on several sources [12, 42,43,44]