Fig. 1.
Pathways across the blood-brain barrier, blood-cerebrospinal fluid barrier, and blood-tumor barrier.
The blood-brain barrier (BBB) is a continuous layer of epithelial cells joined by high-resistance tight junctions surrounded by pericytes and sealed by astrocytic perivascular endfeet.7 , 14 The blood-cerebrospinal fluid (CSF) barrier demarcates the space between the choroid plexus and CSF. Unlike the BBB capillaries, the functional unit of the choroid plexus is fenestrated, has no tight junctions, and thus facilitates molecular transport such as CSF bulk flow, metabolic inactivation, and transcapillary exchange. The blood-tumor barrier refers to a tumor’s vasculature that is a variously permeable barrier. Similar to the BBB, it is a major factor limiting the access of many therapeutic agents to brain tumors.182 The blood-tumor barrier consists of continuous, nonfenestrated capillaries (like those of normal brain), fenestrated capillaries, and interendothelial gaps.182 Expression of efflux transporters located at the blood-tumor barrier represents an additional mechanism that prevents intracellular penetration of anticancer drugs.183 (Brain with tumor adapted with permission under a Creative Commons Attribution License from OpenStax College, http://legacy.cnx.org/content/m45981/1.4/; blood-brain barrier reused with permission under a Creative Commons Attribution License from Kübelbeck A, https://commons.wikimedia.org/wiki/File:Blood-brain_barrier_transport_en.png; anatomy of tight junction adapted with permission under a Creative Commons Attribution License from Polakis P. J Cell Biol. 2008;183(3):371–373; blood CSF barrier adapted with permission under a Creative Commons Attribution License from Bhaskar S, et al. Part Fibre Toxicol. 2010;7:3; blood-tumor barrier adapted from Bredel M. Anticancer drug resistance in primary human brain tumors. Brain Res Brain Res Rev. 2001;35(2):161–204, with permission from Elsevier.)