title: Permeability of endothelial and astrocyte cocultures: in vitro blood-brain barrier models for drug delivery studies.
abstract: The blood-brain barrier (BBB) is a major obstacle for drug delivery to the brain. To seek for in vitro BBB models that are more accessible than animals for investigating drug transport across the BBB, we compared four in vitro cultured cell models: endothelial monoculture (bEnd3 cell line), coculture of bEnd3 and primary rat astrocytes (coculture), coculture with collagen type I and IV mixture, and coculture with Matrigel. The expression of the BBB tight junction proteins in these in vitro models was assessed using RT-PCR and immunofluorescence. We also quantified the hydraulic conductivity (L (p)), transendothelial electrical resistance (TER) and diffusive solute permeability (P) of these models to three solutes: TAMRA, Dextran 10K and Dextran 70K. Our results show that L (p) and P of the endothelial monoculture and coculture models are not different from each other. Compared with in vivo permeability data from rat pial microvessels, P of the endothelial monoculture and coculture models are not significantly different from in vivo data for Dextran 70K, but they are 2-4 times higher for TAMRA and Dextran 10K. This suggests that the endothelial monoculture and all of the coculture models are fairly good models for studying the transport of relatively large solutes across the BBB.
authors.affiliation: Department of Biomedical Engineering, The City College of the City University of New York, New York, NY 10031, USA.
authors.forename: Guanglei
authors.initials: G
authors.lastname: Li
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Simon
authors.forename: Limary M
authors.initials: LM
authors.lastname: Cancel
authors.forename: Zhong-Dong
authors.initials: ZD
authors.lastname: Shi
authors.forename: Xinying
authors.initials: X
authors.lastname: Ji
authors.forename: John M
authors.initials: JM
authors.lastname: Tarbell
authors.forename: Barclay
authors.initials: B
authors.lastname: Morrison
authors.forename: Bingmei M
authors.initials: BM
authors.lastname: Fu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D004341:Drug Evaluation; D017097:Electric Impedance; D004727:Endothelium / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D052250:Nitric Oxide Synthase Type III; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019108:Tight Junctions / Q000378:metabolism
chemical_list: C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III