Tornabene Erica, Brodin Birger
Section of Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
Section of Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
J Pharm Sci. 2016 Feb;105(2):398-405. doi: 10.1016/j.xphs.2015.11.041.
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.
中风是全球范围内导致死亡和残疾的主要原因。脑灌注不足和局灶性脑梗死均由脑血流量减少引起，进而导致中风及随后的脑损伤。目前，中风的药物治疗方法寥寥无几，美国食品药品监督管理局批准的用于治疗急性缺血性中风的组织纤溶酶原激活剂是最突出的例子。大量用于治疗缺血性脑组织的潜在候选药物已被研发出来，但随后在临床试验中失败。深入了解缺血及缺血后脑内皮屏障的渗透途径对于开发新的医学治疗方法至关重要。血脑屏障，即衬于脑毛细血管的内皮单层，在缺血事件期间会改变其特性。血脑屏障的体外模型是在可控条件下研究诱导缺血影响的有用工具。在本综述中，我们旨在简要概述缺血的体外模型。特别关注缺血及缺血后内皮中摄取和外排转运途径的表达。最后，我们将指出脑缺血体外模型领域未来面临的挑战。
