Endothelial cell biology and the enigma of transcytosis through the blood-brain barrier.

The mammalian blood-brain barrier (BBB) to non-lipid soluble macromolecules is associated morphologically with two basic cell types: the cerebral, non-fenestrated endothelium and perivascular phagocytes; the latter is represented by macrophages, microglia and pericytes surrounded by a basal lamina and located on the abluminal surfaces of cerebral arterioles, venules, and less so capillaries (1). Characteristics of the cerebral endothelium serving to define the BBB include circumferential belts of interendothelial tight junctional complexes that preclude the bidirectional, extracellular movement of macromolecules between blood and brain, and acid hydrolase-containing secondary lysosomes (4). The perivascular phagocytes also contain populations of secondary lysosomes and represent the first line of defense once the BBB is breached normally, experimentally, or pathologically (1, 10). In vitro and in vivo data implicate a third cell type, the astrocyte, in influencing the formation of interendothelial tight junctions; however, astrocytes arid their perivascular endfeet are not a physical or morphologically defined-barrier to the extracellular movement of macromolecules between the endothelium and brain parenchyma.