ABSTRACT
The endothelium of the brain vasculature is so impermeable that it is referred to as the blood-brain barrier (BBB). Although the endothelial cells form the primary barrier between the bloodstream and the brain parenchyma, many other cells of the so-called neurovascular unit interact dynamically with the endothelial cells to create a unique brain microenvironment. It is this microenvironment that elicits the barrier phenotype of brain blood vessels. Perivascular cells including smooth muscle, pericytes, astrocytes, neurons, and microglia interact with the endothelial cells to help maintain brain homeostasis. A complicated network of physical contacts and soluble messengers mediates the interactions between multiple cell types. In addition, information does not flow only from perivascular cells to endothelial cells, but the endothelial cells can also promote responses from its surroundings. The former interaction paradigm has been the principal focus of BBB researchers to date, while the latter has been studied to a much lesser extent. The barrier also responds in a spatial and temporally discriminate fashion under neurological disease conditions. The fact that the brain vasculature is restrictive has been known for over 100 years, and significant research effort has identified many BBB attributes. However, the complexity of the interconnected neurovascular unit has thus far limited advances in BBB
knowledge. Because of this, the detailed structure-function relationship of this critical interface remains largely unrefined.
