Department of (Neuro) Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.
Adv Drug Deliv Rev. 2012 Jul;64(10):919-29. doi: 10.1016/j.addr.2011.11.008. Epub 2011 Nov 29.
Over-expression of drug efflux transporters at the level of the blood-brain barrier (BBB) has been proposed as a mechanism responsible for multidrug resistance. Drug transporters in epileptogenic tissue are not only expressed in endothelial cells at the BBB, but also in other brain parenchymal cells, such as astrocytes, microglia and neurons, suggesting a complex cell type-specific regulation under pathological conditions associated with epilepsy. This review focuses on the cerebral expression patterns of several classes of well-known membrane drug transporters such as P-glycoprotein (Pgp), and multidrug resistance-associated proteins (MRPs) in the epileptogenic brain. Both experimental and clinical evidence of epilepsy-associated cerebral drug transporter regulation and the possible mechanisms underlying drug transporter regulation are discussed. Knowledge of the cerebral expression patterns of drug transporters in normal and epileptogenic brain will provide relevant information to guide strategies attempting to overcome drug resistance by targeting specific transporters.
血脑屏障（BBB）中药物外排转运体的过度表达被认为是多药耐药的机制之一。致痫组织中的药物转运体不仅在 BBB 的内皮细胞中表达，而且在其他脑实质细胞如星形胶质细胞、小胶质细胞和神经元中表达，提示与癫痫相关的病理条件下存在复杂的细胞类型特异性调节。本文综述了几种已知的膜药物转运体在致痫脑中的脑表达模式，如 P-糖蛋白（Pgp）和多药耐药相关蛋白（MRPs）。讨论了癫痫相关脑药物转运体调节的实验和临床证据，以及药物转运体调节的可能机制。了解正常和致痫脑中药物转运体的脑表达模式将为通过靶向特定转运体来克服耐药性的策略提供相关信息。
