Understanding the rules of the road: proteomic approaches to interrogate the blood brain barrier

The blood brain barrier (BBB) is often regarded as a passive barrier that protects brain parenchyma from toxic substances, circulating leukocytes, while allowing the passage of selected molecules. Recently, a combination of molecular profiling techniques have characterized the constituents of the BBB based on in vitro models using isolated endothelial cells and ex vivo models analyzing isolated blood vessels. Characterization of gene expression profiles that are specific to the endothelium of brain blood vessels, and the identification of proteins, cells and multi-cellular structure that comprise the BBB have led to a emerging consensus that the BBB is not, in and of itself, a simple barrier of specialized endothelial cells. Instead, regulation of transcytosis, permeability, and drug translocation into the central nervous system is now viewed as a collection of neurovascular units (NVUs) that, together, give the BBB its unique biological properties. We will review recent technology advancing the understanding of the molecular basis of the BBB with a focus on proteomic approaches.