HYDROCORTISONE REINFORCES THE BLOOD-BRAIN-BARRIER PROPERTIES IN A SERUM-FREE CELL-CULTURE SYSTEM

The increasing number of newly developed drugs demands for functional in vitro models of the blood-brain barrier to determine their brain up take. Cultured cerebral capillary endothelial cells are considered to be such a model, however in serum containing media they exhibit low el ectrical resistances and high permeabilities compared to the in vivo s ituation. Here we report the establishment of a serum-free cell cultur e model. Withdrawal of serum already caused a twofold increase of tran sendothelial resistance (TER), which in presence of serum is about 100 -150 Ohm . cm(2). We tested several supplements and found that hydroco rtisone is a potent stimulator for the formation of barrier properties . TERs up to 1000 Ohm . cm(2) were measured in the presence of physiol ogical relevant hydrocortisone concentrations. In correspondence to th e TER increase hydrocortisone decreased cell monolayer permeability fo r sucrose down to 5 . 10(-7) cm/s, which is close to the in vivo value of 1.2 . 10(-7) cm/s and by a factor of five lower compared to cultur es without hydrocortisone and in presence of serum. (C) 1998 Academic Press.