Chapter title |
A Simple Adaptable Blood-Brain Barrier Cell Model for Screening Matrix Metalloproteinase Inhibitor Functionality
|
---|---|
Chapter number | 16 |
Book title |
Matrix Metalloproteases
|
Published in |
Methods in molecular biology, March 2017
|
DOI | 10.1007/978-1-4939-6863-3_16 |
Pubmed ID | |
Book ISBNs |
978-1-4939-6861-9, 978-1-4939-6863-3
|
Authors |
Jennifer S. Myers, Joan Hare, Qing-Xiang Amy Sang |
Editors |
Charles A. Galea |
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. |
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