title: A Simple Adaptable Blood-Brain Barrier Cell Model for Screening Matrix Metalloproteinase Inhibitor Functionality.
abstract: The blood-brain barrier is a multicellular and basement membrane unit that regulates molecular transport between the blood and central nervous system. Many cerebral pathologies, such as acute stroke and chronic vascular dementia, result in a disrupted blood-brain barrier, increasing its permeability and allowing the entry of potentially neurotoxic molecules. The activation of matrix metalloproteinases mediates further blood-brain barrier damage. The inhibition of matrix metalloproteinases is a potential strategy for stroke therapy. As inhibitors are developed, efficient context-specific screening methods will be required. Models of the blood-brain barrier have been extensively used to study neuropathologies and the effect of various treatment options.Herein, we describe a co-culture model of the blood-brain barrier composed of brain microvascular endothelial cells and astrocytes grown on an artificial basement membrane-coated membrane insert. Our cell model forms a barrier and is a simple first approximation of blood-brain barrier integrity. As currently developed, the model may be applied to testing the effect of matrix metalloproteinases and matrix metalloproteinase inhibitors on blood-brain barrier physiology and pathophysiology. The model is a quick and effective evaluation tool for generating nonclinical data in a living cell system before proceeding to animal models.
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Myers
authors.affiliation: Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Hare
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL, USA. qxsang@chem.fsu.edu.|Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, USA. qxsang@chem.fsu.edu.
authors.forename: Qing-Xiang Amy
authors.initials: QA
authors.lastname: Sang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply; D002417:Cattle; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors / Q000493:pharmacokinetics; D008954:Models, Biological
chemical_list: D061965:Matrix Metalloproteinase Inhibitors
keywords: BBB co-culture model; BBB permeability; Blood-brain barrier; Bovine brain microvascular endothelial cells; Cell culture membrane inserts; Matrix-metalloproteinase inhibitors; Matrix-metalloproteinases; Normal human astrocytes; Stroke; Tissue plasminogen activator