School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands.
European Graduate School of Neuroscience (EURON), Maastricht, the Netherlands.
Mol Neurobiol. 2018 Apr;55(4):2780-2788. doi: 10.1007/s12035-017-0501-y. Epub 2017 Apr 28.
Drug delivery to the central nervous system (CNS) is complicated by the blood-brain barrier. As a result, many agents that are found to be potentially effective at their site of action cannot be sufficiently or effectively delivered to the CNS and therefore have been discarded and not developed further for clinical use, leaving many CNS diseases untreated. One way to overcome this obstacle is intracerebroventricular (ICV) delivery of the therapeutics directly to cerebrospinal fluid (CSF). Recent experimental and clinical findings reveal that CSF flows from the ventricles throughout the parenchyma towards the subarachnoid space also named minor CSF pathway, while earlier, it was suggested that only in pathological conditions such as hydrocephalus this form of CSF flow occurs. This transependymal flow of CSF provides a route to distribute ICV-infused drugs throughout the brain. More insight on transependymal CSF flow will direct more rational to ICV drug delivery and broaden its clinical indications in managing CNS diseases.
药物递送至中枢神经系统（CNS）较为复杂，这是由于血脑屏障的存在。结果，许多在作用部位具有潜在疗效的药物无法充分或有效地递送至 CNS，因此被摒弃，并未进一步开发用于临床应用，导致许多 CNS 疾病未得到治疗。克服这一障碍的一种方法是将治疗剂通过脑室内（ICV）直接递送至脑脊液（CSF）。最近的实验和临床研究结果表明，CSF 从脑室沿着脑实质流向蛛网膜下腔，也称为小 CSF 通路，而早期，人们认为只有在脑积水等病理情况下才会出现这种 CSF 流动形式。这种穿过室管膜的 CSF 流动为将 ICV 输注的药物分布到整个大脑提供了一种途径。对穿透室管膜 CSF 流动的更多了解将指导更合理的 ICV 药物递送，并拓宽其在治疗 CNS 疾病方面的临床适应证。
