title: Patented in vitro blood-brain barrier models in CNS drug discovery.
abstract: The blood-brain barrier (BBB) is a regulatory interface between the circulation and the central nervous system (CNS). Therapy of neurological diseases is limited due to restricted penetration of pharmacons across the BBB. Models for screening the brain penetration of drug candidates are needed early in drug discovery. Culture-based models are useful tools for both basic research on BBB, and testing the permeability of new therapeutical molecules. This review focuses on patented in vitro BBB models and their potential application in CNS drug discovery. Cell culture models using primary and immortalized brain endothelial cells of non-human and human origin, in co-culture or mono-culture setting, in static or dynamic conditions are discussed, as well as methods to induce BBB properties in such in vitro models. The aim of these models is to reproduce as many aspects as possible of the in vivo BBB. All models should show some elements of general endothelial and specific BBB properties, like physiologically realistic cell architecture, restrictive paracellular pathway, and functional expression of transport mechanisms. Though no "ideal in vitro BBB model" has been constructed yet, the currently available models provide valuable information on BBB permeability and are useful tools in CNS drug discovery.
authors.affiliation: Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary. deli@brc.hu.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tóth
authors.forename: Szilvia
authors.initials: S
authors.lastname: Veszelka
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Masami
authors.initials: M
authors.lastname: Niwa
authors.forename: Mária A
authors.initials: MA
authors.lastname: Deli
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D002460:Cell Line; D002491:Central Nervous System Agents / Q000493:pharmacokinetics*; D018920:Coculture Techniques; D000242:Cyclic AMP / Q000502:physiology; D055808:Drug Discovery; D006801:Humans; D010330:Patents as Topic; D033081:Shear Strength; D015398:Signal Transduction; D051153:Wnt Proteins / Q000502:physiology
chemical_list: D002491:Central Nervous System Agents; D051153:Wnt Proteins; D000242:Cyclic AMP