UC San Diego

The blood-brain barrier (BBB) is a multi-cellular vascular structure in the central nervous system that separates the circulating blood from the brain parenchyma. It is composed of microvessels made of endothelial cells with tight intercellular junctions surrounded by a basal lamina, astrocytes, and pericytes. In many diseased states of the brain, the integrity of the BBB is compromised and the changes in protein levels of key regulators such as transporters leave the brain open for attack. Previous studies have generated detailed databases of the microvessel transcriptome, however, less information is available on the BBB at the protein level. The focus of this study is not to elucidate on proteins that are already widely known and are hallmarks of the BBB but to generate a more extensive protein database of relatively unknown and unique proteins that can be used to gain further insight into the structure and function of the BBB. We specifically focused on the characterization of the membrane fraction of cells within the BBB to generate a more complete understanding of membrane transporters, tight junction proteins, and associated extracellular matrix proteins. Using Multidimensional Protein Identification Technology. 53% out of a total of 1,143 proteins found in mouse brain microvessels were determined to be membrane-associated. Analyses of specific classes of BBB-associated proteins in the context of recent transcriptome and proteome reports provides a unique database to assess the relative contribution of genes at the RNA and protein level in the maintenance of normal BBB integrity