Control of the blood-brain barrier by glucocorticoids and the cells of the neurovascular unit

Abstract

The blood-brain barrier is built up by endothelial cells lining the cerebral capillaries whereby the physical diffusion barrier is formed by tight junctions sealing the intercellular clefts. Chemical factors being released endogenously to the blood stream may regulate the barrier tightness. However, since tight junctions of the cerebral capillaries are more complex compared to those of other vessels, it becomes evident that the cells of the neurovascular unit play an important role in the induction and the maintenance of the barrier properties. Astrocytes and pericytes interact with the endothelial cells whereby the contact zone is built up by the extracellular matrix. Thus, in addition to chemical mediators released from either cells of the cerebrovascular unit leading to a crosstalk between those cells, the presence of given molecules of the extracellular matrix and also their assembly have to be considered in the transfer of signals able to induce or modulate the barrier. Here we report and summarize recent evidence that external factors like glucocorticoids act in concert with astroyctes in a co-culture system of primary porcine endothelial cells with astrocytes, but only if astrocytes are able to contact the endothelial cells. Moreover, evidence will be given to show that astrocytic and also the pericytic extracellular matrix produced by those cells are able to induce the barrier by an upregulation of the tight junction proteins occludin, claudin-5 and ZO-1, both on mRNA and at the protein level. © 2009 New York Academy of Sciences.