Abstract
The blood-brain barrier possesses active transporters carrying brain-permeable xenobiotics back into the blood against concentration gradients. We demonstrate that multidrug resistance transporter (Mdr)-1 is upregulated on capillary endothelium after focal cerebral ischemia; moreover, Mdr-1 deactivation by pharmacological inhibition or genetic knockout preferably enhances the accumulation and efficacy of two neuroprotectants known as Mdr-1 substrates in the ischemic brain. We predict that Mdr-1 inhibition may greatly facilitate neuroprotective therapies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
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Animals
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Blood-Brain Barrier / physiology
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Brain / anatomy & histology
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Brain / physiology
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Brain Ischemia / drug therapy*
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Brain Ischemia / metabolism
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Brain Ischemia / pathology
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Capillaries / cytology
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Capillaries / metabolism
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Cerebrovascular Circulation / physiology
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Endothelium, Vascular / metabolism
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Enzyme Inhibitors / metabolism
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Immunosuppressive Agents / metabolism
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Mice
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Mice, Knockout
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Neuroprotective Agents / therapeutic use*
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Quinolines / metabolism*
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Rifampin / metabolism
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Tacrolimus / metabolism
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Enzyme Inhibitors
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Immunosuppressive Agents
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Neuroprotective Agents
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Quinolines
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tariquidar
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Rifampin
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Tacrolimus