Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2487622 | Journal of Pharmaceutical Sciences | 2007 | 18 Pages |
Abstract
The purpose of the study was to assess the suitability of the mouse endothelial cell line bEnd5 as a blood-brain barrier (BBB) model under normal or pathologic (stroke) conditions. In comparison to the wellâestablished bovine brain endothelial cell (BBMEC) model, cultured bEnd5 monolayers reached a maximal transendothelial electrical resistance (TEER) of 121 Ω cm2 on day 7, and possessed oval and spindle shape morphology. Structurally, confluent monolayers of bEnd5 cells and BBMECs exhibit peripheral band staining of the tight junction protein ZOâ1 and occludin. Both bEnd5 and BBMECs express important tight junctional proteins, ZOâ1, occludin and claudinâ1, as well as the transporters Pâglycoprotein (Pâgp), NKCC, GLUT1, and most PKC isoforms. Marker permeability experiments suggest that bEnd5 cells form a tight barrier that compares to wellâestablished in vitro BBB models, such as the BBMEC. After short durations of hypoxia/aglycemia (H/A), hyperpermeability was seen in the bEnd5 endothelial monolayer compared to later time periods for BBMECs, suggesting that bEnd5 cells are more sensitive to hypoxia/algycemia treatment than BBMECs. Taken together, bEnd5 cell culture model may provide a useful in vitro model of the BBB for drug delivery studies and modeling pathological states such as oxygen glucose deprivation associated with stroke. © 2007 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3196-3213, 2007
Keywords
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Tianzhi Yang, Karen E. Roder, Thomas J. Abbruscato,