Johanson Conrad E, Duncan John A, Stopa Edward G, Baird Andrew
Department of Clinical Neurosciences, Rhode Island Hospital, Brown Medical School, Providence, Rhode Island 02912, USA.
Pharm Res. 2005 Jul;22(7):1011-37. doi: 10.1007/s11095-005-6039-0. Epub 2005 Jul 22.
The choroid plexus (CP), i.e., the blood-cerebrospinal fluid barrier (BCSFB) interface, is an epithelial boundary exploitable for drug delivery to brain. Agents transported from blood to lateral ventricles are convected by CSF volume transmission (bulk flow) to many periventricular targets. These include the caudate, hippocampus, specialized circumventricular organs, hypothalamus, and the downstream pia-glia and arachnoid membranes. The CSF circulatory system normally provides micronutrients, neurotrophins, hormones, neuropeptides, and growth factors extensively to neuronal networks. Therefore, drugs directed to CSF can modulate a variety of endocrine, immunologic, and behavioral phenomema; and can help to restore brain interstitial and cellular homeostasis disrupted by disease and trauma. This review integrates information from animal models that demonstrates marked physiologic effects of substances introduced into the ventricular system. It also recapitulates how pharmacologic agents administered into the CSF system prevent disease or enhance the brain's ability to recover from chemical and physical insults. In regard to drug distribution in the CNS, the BCSFB interaction with the blood-brain barrier is discussed. With a view toward translational CSF pharmacotherapy, there are several promising innovations in progress: bone marrow cell infusions, CP encapsulation and transplants, neural stem cell augmentation, phage display of peptide ligands for CP epithelium, CSF gene transfer, regulation of leukocyte and cytokine trafficking at the BCSFB, and the purification of neurotoxic CSF in degenerative states. The progressively increasing pharmacological significance of the CP-CSF nexus is analyzed in light of treating AIDS, multiple sclerosis, stroke, hydrocephalus, and Alzheimer's disease.
脉络丛（CP），即血脑脊髓液屏障（BCSFB）界面，是可用于向脑内递送药物的上皮边界。从血液转运至侧脑室的药物通过脑脊液容量传输（ bulk flow）对流至许多脑室周围靶点。这些靶点包括尾状核、海马体、特殊的室周器官、下丘脑以及下游的软脑膜-胶质细胞和蛛网膜。脑脊液循环系统通常广泛地为神经网络提供微量营养素、神经营养因子、激素、神经肽和生长因子。因此，针对脑脊液的药物可调节多种内分泌、免疫和行为现象；并有助于恢复因疾病和创伤而破坏的脑间质和细胞内稳态。本综述整合了来自动物模型的信息，这些信息证明了引入脑室系统的物质具有显著的生理效应。它还概述了向脑脊液系统给药的药物制剂如何预防疾病或增强大脑从化学和物理损伤中恢复的能力。关于药物在中枢神经系统中的分布，讨论了BCSFB与血脑屏障的相互作用。展望转化性脑脊液药物治疗，目前有几项有前景的创新正在进行中：骨髓细胞输注、脉络丛封装和移植、神经干细胞扩增、针对脉络丛上皮的肽配体的噬菌体展示、脑脊液基因转移、在BCSFB处调节白细胞和细胞因子的运输以及在退行性状态下纯化神经毒性脑脊液。根据治疗艾滋病、多发性硬化症、中风、脑积水和阿尔茨海默病的情况，分析了脉络丛-脑脊液联系在药理学上日益增加的重要性。
