It has recently been shown that the endothelial cells in brain capillaries are the anatomic site of the blood-brain barrier, and that these endothelial cells act to maintain a constant composition and volume of brain interstitial fluid.1-3 Defects in brain capillary function appear to play a role in the pathogenesis of brain edema and hemorrhage in a wide variety of diseases. Conditions as diverse as intraventricular hemorrhage of the premature, asphyxia neonatorum, lead poisoning, head injury, Reye's syndrome, osmolar coma, and the brain edema surrounding a tumor or abscess may all share the common feature of brain capillary failure. In this review, I will consider some recent advances in our understanding of the brain microvasculature that may explain their unusual susceptibility to injury.
Brain capillaries have a number of important differences from capillaries in other organs. A schematic of a typical brain capillary is shown in the Figure. Unlike systemic capillaries, the endothelial cells in brain capillaries are joined together by tight junctions.3 These cellular junctions are present around the entire circumference of the capillary tube. The result is a continuous layer of endothelial cells that effectively separate the plasma from the interstitial fluid of the brain. The tight junctions are composed of a series of complex interdigitations that create a barrier so complete that water-soluble molecules and ions are unable to move into the brain between the endothelial cells. In other organs, the capillaries do not have tight junctions, and sugars, amino acids, ions, and drugs readily diffuse between endothelial cells into the interstitial fluid.
Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice
