Permeability of in vitro blood-brain barrier models

The blood-brain barrier (BBB) is a major obstacle for drug delivery to the brain for treatment of CNS disorders. To search for more convenient models in studying the transport across the BBB, we compared four in vitro models: endothelial monoculture (bEnd3 cell line), coculture of bEnd3 and astrocytes (coculture), coculture with collagen type I and IV mixture, and coculture with Matrigel. We also quantified the hydraulic conductivity (Lp), trans-electrical resistance (TER) and diffusive permeability (P) of these models to three solutes: TAMRA, Dextran 10K and Dextran70K. Our results showed that Lp and P of the endothelial monolayer and coculture models are not different from each other. Compared with in vivo permeability data from rat pial microvessels [1], P of the endothelial monolayer and coculture models are not significantly different from in vivo data for Dextran 70K while they are 2-4 times higher for TAMRA and Dextran 10K. The results suggested that endothelial monolayer and all the coculture models are fairly good models for studying transport of relatively large solutes across the BBB.