Studies of pathophysiological mechanisms of blood-brain barrier (BBB) disturbances have been hampered by the functional interrelationship existing between various cerebral elements and particularly by the simultaneous changes of many parameters occurring during pathological events in-vivo. An in-vitro model has been developed to investigate 'barrier' functions in cultured cerebromicrovascular endothelium under controlled conditions. Changes in endothelial permeability were tested by exposing the cells to 1) hypertonic solution (known to alter the BBB permeability in-vivo), and 2) agents which have been implicated in mediating brain edema. 1) Hypertonic solution (400 mosm/1) increased significantly the endothelial permeability to trypan blue without apparent decrease of cellular viability when compared to isotonic medium. 2) High concentration of arachidonic acid [(100 MuM), the prostaglandin precursor] almost completely disruptedthe endothelial 'barrier' while lower levels of this substance (10 MuM) increased the cellular permeability to trypan blue only in the presence of indomethacin (10 MuM), the known inhibitor of prostaglandin synthesis. However, indomethacin alone in high concentrations (100 MuM) also enhanced the endothelial permeability to trypan blue.
