Role of Transporters in Central Nervous System Drug Delivery and Blood-Brain Barrier Protection: Relevance to Treatment of Stroke

Journal of Central Nervous System Disease

Review

Kathryn Ibbotson¹  Hrvoje Brzica²  Wazir Abdullahi²  Patrick T Ronaldson² 

[1] Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ, USA;Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ, USA;

关键词: Ischemic stroke;    blood-brain barrier;    solute carrier (SLC) transporters;    ATP-binding cassette (ABC) transporters;    neuroprotection;    vascular protection;    glutathione;   

DOI  :  10.1177/1179573517693802

 received in 2016-08-29, accepted in 2017-01-22,  发布年份 2017

来源: Sage Journals

【 摘 要 】

Ischemic stroke is a leading cause of morbidity and mortality in the United States. The only approved pharmacologic treatment for ischemic stroke is thrombolysis via recombinant tissue plasminogen activator (r-tPA). A short therapeutic window and serious adverse events (ie, hemorrhage, excitotoxicity) greatly limit r-tPA therapy, which indicates an essential need to develop novel stroke treatment paradigms. Transporters expressed at the blood-brain barrier (BBB) provide a significant opportunity to advance stroke therapy via central nervous system delivery of drugs that have neuroprotective properties. Examples of such transporters include organic anion–transporting polypeptides (Oatps) and organic cation transporters (Octs). In addition, multidrug resistance proteins (Mrps) are transporter targets in brain microvascular endothelial cells that can be exploited to preserve BBB integrity in the setting of stroke. Here, we review current knowledge on stroke pharmacotherapy and demonstrate how endogenous BBB transporters can be targeted for improvement of ischemic stroke treatment.

【 授权许可】

CC BY-NC   
© The Author(s) 2017

【 图 表 】

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