Figure 3.

A. Schematic representation of the blood–brain barrier. The blood–brain barrier is formed primarily by brain endothelial cells in capillaries and is regulated by surrounding pericytes and astrocytes at the basolateral side of the endothelial cells. The endothelial cells form tight junctions, mediated by connexin, occludin, and claudin family proteins. At the apical cell surface, ABC transporters such as P-gp (P-glycoprotein, ABCB1), ABCG2 (also breast cancer resistance protein), and MRP4 (multidrug-resistance protein 4, ABCC4) transport small molecules back into the lumen. Ingress of nutrients from the blood supply is mediated by facilitative solute carrier SLC transporters, such as glutamate (excitatory amino acid transporter 1, Eaat1, SLC1A3) and D-glucose (glucose uptake transporter 1, Glut1, SLC2A1). Lining the apical surface and projecting into the lumen is the glycocalyx (not shown), composed of glycoprotein and polysaccharide. This panel was reprinted by permission from Springer Nature ⁴⁶: ABC Transporters - 40 Years On, Basseville et al., The ABCG2 multidrug transporter, 2016. [ https://link.springer.com/chapter/10.1007/978-3-319-23476-2_9]. B. Zebrafish homologs of human P-glycoprotein (P-gp) are expressed at the blood–brain barrier. Expression of zebrafish homologs of P-gp were determined by immunohistochemistry staining with the C219 antibody on formalin-fixed, paraffin-embedded zebrafish. Staining is found in the vasculature of the zebrafish brain.