Volume Regulation of the in Vitro Blood-Brain Barrier by Osmoreactive Amino Acids during Stress

Abstract

The blood-brain barrier (BBB) is more permeable to blood-borne compounds during stress or disease. Moreover, during stress, an extra demand is put on the regulatory systems for the maintenance of cell volume. Hence, the ability of the brain capillary endothelial cells (BCEC) to regulate their volume is essential for maintaining the integrity of the BBB. In this study, the effect of stress on BCEC was investigated by means of osmolyte efflux measurements (free amino acids) into the extracellular fluid (eg., the culture medium). Extracellular concentrations of aspartic acid, glutamic acid, taurine and glycine increased several fold, while glutamine and serine showed no change in extracellular concentration after exposure to stress. This experiment showed that the volume regulatory response of stressed BCEC is, at least partially, dependent on the efflux of free amino acids. By determining the mechanism by which the volume regulation of these cells is controlled, we anticipate to have a tool by which we can modulate the permeability of the BBB in disease state (eg., vasogenic edema or CNS inflammation).