Lefauconnier J M, Hauw J J
Rev Neurol (Paris). 1984;140(2):89-109.
The first part of this review was concerned with morphological data. The second part dealt with the general mechanisms and methods of study of the transport of low molecular weight substances, and with water and electrolytes transport. In this third part, the transport of hydrophilic and lipophilic substances, drugs and neurotransmitters is reviewed. In addition, the developmental characteristics of the BBB and its regulation are described. Hydrophilic substances cannot penetrate the lipid walls unless they are transported through the membranes by a proteinic carrier process. Thus far 9 carrier transport systems have been described for the brain capillaries: 1 for hexoses, 4 for amino acids, 1 for short chain monocarboxylic acids, 2 for nucleic acid precursors and 1 for choline. The blood-brain transport step may play an important role in metabolic utilization of some of these substrates by the brain. The penetration of lipophilic substances across the BBB is dependent upon the following four factors: 1) lipophilia of their undissociated form, (accounted for in their oil/water coefficient); 2) ionic dissociation at plasma pH (only the undissociated form is able to cross the membrane); 3) binding to plasma proteins; 4) molecular weight. The penetration of drugs into the central nervous system is dependent upon these 4 factors. Several trials have been made to enable the passage of normally excluded substances of pharmacological interest: in situ injection; administration of pro-drugs and of liposomes; osmotic opening of the BBB. The peripheral pool of neurotransmitters seems to be totally excluded from the brain by an enzymatic barrier which catabolizes those which have entered the endothelial cell and thus enhances the barrier effect of the endothelial cell luminal membrane. Developmental modifications in the properties of the BBB are observed. The permeability of the BBB in the young can no longer be considered as unselectively greater than in the adult. Although more permeable to some solutes it is less permeable to others, which perhaps reflects a difference in the metabolic needs of immature and adult brains. The permeability of the choroid plexus falls under peripheral regulation. Such regulation (which might also be central) is suggested for brain capillaries based upon the results of physiologic experiments and the existence on their membranes of receptors to neurotransmitters and of neurotransmitter-stimulated adenylate-cyclase.
本综述的第一部分涉及形态学数据。第二部分论述了低分子量物质运输以及水和电解质运输的一般机制与研究方法。在这第三部分中，将对亲水性和亲脂性物质、药物及神经递质的运输进行综述。此外，还将描述血脑屏障的发育特征及其调控。亲水性物质除非通过蛋白质载体过程跨膜运输，否则无法穿透脂质壁。迄今为止，已描述了9种脑毛细血管的载体运输系统：1种用于己糖，4种用于氨基酸，1种用于短链单羧酸，2种用于核酸前体，1种用于胆碱。血脑运输步骤可能在大脑对其中一些底物的代谢利用中发挥重要作用。亲脂性物质穿越血脑屏障取决于以下四个因素：1）其未解离形式的亲脂性（由其油/水系数表示）；2）在血浆pH值下的离子解离（只有未解离形式能够穿过膜）；3）与血浆蛋白的结合；4）分子量。药物进入中枢神经系统取决于这四个因素。已经进行了多项试验以使具有药理学意义的通常被排除的物质能够通过：原位注射；前体药物和脂质体的给药；血脑屏障的渗透性开放。神经递质的外周库似乎被一种酶屏障完全排除在大脑之外，这种酶屏障会分解进入内皮细胞的神经递质，从而增强内皮细胞腔面膜的屏障作用。观察到血脑屏障特性的发育变化。幼年期血脑屏障的通透性不再被认为比成年期无选择性地更高。尽管它对某些溶质的通透性更高，但对其他溶质的通透性更低，这可能反映了未成熟和成年大脑代谢需求的差异。脉络丛的通透性受外周调节。基于生理学实验结果以及其膜上存在神经递质受体和神经递质刺激的腺苷酸环化酶，推测脑毛细血管也存在这种调节（可能也是中枢性的）。
