Hydrocortisone reinforces the blood-brain 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 uptake. Cultured cerebral capillary endothelial cells are considered to be such a model, however in serum containing media they exhibit low electrical resistances and high permeabilities compared to the in vivo situation. Here we report the establishment of a serum-free cell culture model. Withdrawal of serum already caused a twofold increase of transendothelial resistance (TER), which in presence of serum is about 100-150 Omega x cm2. We tested several supplements and found that hydrocortisone is a potent stimulator for the formation of barrier properties. TERs up to 1000 Omega x cm2 were measured in the presence of physiological relevant hydrocortisone concentrations. In correspondence to the TER increase hydrocortisone decreased cell monolayer permeability for sucrose down to 5x10(-7) cm/s, which is close to the in vivo value of 1.2x10(-7) cm/s and by a factor of five lower compared to cultures without hydrocortisone and in presence of serum.