Decreased blood-brain barrier permeability to fluorescein in streptozotocin-treated rats
| Autor: | Scott M. Ocheltree, Kristi M. Norwood, Brian T. Hawkins, Richard D. Egleton |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty ATP Binding Cassette Transporter Subfamily B Time Factors Organic anion transporter 1 Blotting Western Fluorescent Antibody Technique Gene Expression Biology Organic Anion Transporters Sodium-Independent Blood–brain barrier Article Streptozocin Capillary Permeability Rats Sprague-Dawley Internal medicine medicine Animals Drug Interactions Transcellular Tight junction General Neuroscience Streptozotocin Transport protein Rats medicine.anatomical_structure Endocrinology Blood-Brain Barrier Paracellular transport biology.protein Fluorescein Efflux medicine.drug |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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