Decreased blood-brain barrier permeability to fluorescein in streptozotocin-treated rats

NEUROSCIENCE LETTERS

卷:411

Article

Hawkins, Brian T. ; Ocheltree, Scott M. ; Norwood, Kristi M. ; Egleton, Richard D.

关键词: blood-brain barrier;    diabetes;    multidrug resistance protein;    organic anion transporter;    fluorescein;    in situ brain perfusion;   

DOI  :  10.1016/j.neulet.2006.09.010

来源: Elsevier

【 摘 要 】

Investigations of the blood-brain barrier (BBB) in diabetes have yielded contradictory results. It is possible that diabetes differentially affects paracellular and transcellular permeabilities via modulation of tight junction and transport proteins, respectively. Fluorescein (FL), a marker for paracellular permeability, is a substrate for the transport proteins organic anion transporter (OAT)-3 and multidrug resistance protein (MRP)-2 at the BBB. Furthermore, MRP-2-mediated efflux of FL can be upregulated by glucose. In this study, streptozotocin-induced diabetes led to decreased brain distribution of FL measured by in situ brain perfusion, consistent with activation of an efflux transport system for FL at the BBB. This change was paralleled by increased protein expression of MRP-2, but not OAT-3, in cerebral microvessels. These data indicate that diabetes may lead to changes in efflux transporters at the BBB and have implications for delivery of therapeutics to the central nervous system. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

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