Stroke and Drug Delivery--In Vitro Models of the Ischemic Blood-Brain Barrier

Abstract

Stroke is a major cause of death and disability worldwide. Both cerebral hypoperfusion and focal cerebral infarcts are caused by a reduction of blood flow to the brain, leading to stroke and subsequent brain damage. At present, only few medical treatments of stroke are available, with the Food and Drug Administration-approved tissue plasminogen activator for treatment of acute ischemic stroke being the most prominent example. A large number of potential drug candidates for treatment of ischemic brain tissue have been developed and subsequently failed in clinical trials. A deeper understanding of permeation pathways across the barrier in ischemic and postischemic brain endothelium is important for development of new medical treatments. The blood-brain barrier, that is, the endothelial monolayer lining the brain capillaries, changes properties during an ischemic event. In vitro models of the blood-brain barrier are useful tools to investigate the effects of induced ischemia under controlled conditions. In the present mini review, we aim to give a brief overview of the in vitro models of ischemia. Special focus is given to the expression of uptake and efflux transport pathways in the ischemic and postischemic endothelium. Finally, we will point toward future challenges within the field of in vitro models of brain ischemia.

Keywords: cell lines; drug transport; efflux pumps; membrane transporter; multidrug resistance transporters; solute transporters; transcellular transport; transporters.