Fig. 2 |. Physical and chemical properties of the BBB.
The blood–brain barrier (BBB) structure displays unique physical properties that tightly regulate molecular and cellular flow in the neuroparenchyma. The brain barrier’s importance is evident from its functional conservation across organisms, from fruit flies to humans1. As the BBB develops and matures, endothelial cell fenestrations decrease, and the subsequent appearance of tight junctions is followed by a reduction in transcytosis. Centre panel: cross-section of a central nervous system (CNS) capillary depicting estimated distances and spaces within the BBB, which circulating drugs are required to overcome to permeate the brain parenchyma. Left panel: in the non-diseased brain, the neurovascular unit (NVU) includes an intact BBB that displays multiple characteristics that limit drug permeability into the CNS. Right panel: during tumour progression, stroma–cancer cell interactions in the brain tumour microenvironment dictate vessel permeability and cancer cell proliferation. The blood–tumour barrier (BTB) characteristics listed here contribute to the heterogeneous permeability observed in the disrupted NVU. BCRP, breast cancer resistance protein; ECM, extracellular matrix; MRP, multidrug resistance protein; P-gp, P-glycoprotein; S1P3, sphingosine 1-phosphate 3.