Hladky Stephen B, Barrand Margery A
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK.
Fluids Barriers CNS. 2016 Oct 31;13(1):19. doi: 10.1186/s12987-016-0040-3.
The two major interfaces separating brain and blood have different primary roles. The choroid plexuses secrete cerebrospinal fluid into the ventricles, accounting for most net fluid entry to the brain. Aquaporin, AQP1, allows water transfer across the apical surface of the choroid epithelium; another protein, perhaps GLUT1, is important on the basolateral surface. Fluid secretion is driven by apical Na-pumps. K secretion occurs via net paracellular influx through relatively leaky tight junctions partially offset by transcellular efflux. The blood-brain barrier lining brain microvasculature, allows passage of O, CO, and glucose as required for brain cell metabolism. Because of high resistance tight junctions between microvascular endothelial cells transport of most polar solutes is greatly restricted. Because solute permeability is low, hydrostatic pressure differences cannot account for net fluid movement; however, water permeability is sufficient for fluid secretion with water following net solute transport. The endothelial cells have ion transporters that, if appropriately arranged, could support fluid secretion. Evidence favours a rate smaller than, but not much smaller than, that of the choroid plexuses. At the blood-brain barrier Na tracer influx into the brain substantially exceeds any possible net flux. The tracer flux may occur primarily by a paracellular route. The blood-brain barrier is the most important interface for maintaining interstitial fluid (ISF) K concentration within tight limits. This is most likely because Na-pumps vary the rate at which K is transported out of ISF in response to small changes in K concentration. There is also evidence for functional regulation of K transporters with chronic changes in plasma concentration. The blood-brain barrier is also important in regulating HCO and pH in ISF: the principles of this regulation are reviewed. Whether the rate of blood-brain barrier HCO transport is slow or fast is discussed critically: a slow transport rate comparable to those of other ions is favoured. In metabolic acidosis and alkalosis variations in HCO concentration and pH are much smaller in ISF than in plasma whereas in respiratory acidosis variations in pH and pH are similar. The key similarities and differences of the two interfaces are summarized.
分隔大脑与血液的两个主要界面具有不同的主要功能。脉络丛向脑室分泌脑脊液，这是进入大脑的大部分净液体的来源。水通道蛋白AQP1允许水穿过脉络丛上皮的顶端表面；另一种蛋白质，可能是GLUT1，在基底外侧表面起重要作用。液体分泌由顶端的钠泵驱动。钾的分泌是通过相对渗漏的紧密连接的细胞旁净内流发生的，这种内流部分被跨细胞外流抵消。脑微血管内衬的血脑屏障允许氧气、二氧化碳和葡萄糖根据脑细胞代谢的需要通过。由于微血管内皮细胞之间存在高电阻紧密连接，大多数极性溶质的转运受到极大限制。由于溶质通透性低，静水压差不能解释净液体移动；然而，水通透性足以支持液体分泌，并随着溶质的净转运而伴随水的移动。内皮细胞有离子转运体，如果排列适当，可以支持液体分泌。有证据表明其速率小于脉络丛，但相差不大。在血脑屏障处钠示踪剂进入大脑的通量大大超过任何可能的净通量。示踪剂通量可能主要通过细胞旁途径发生。血脑屏障是将细胞间液（ISF）钾浓度维持在严格范围内的最重要界面。这很可能是因为钠泵会根据钾浓度的微小变化改变钾从ISF中转运出的速率。也有证据表明钾转运体随血浆浓度的慢性变化而进行功能调节。血脑屏障在调节ISF中的HCO和pH方面也很重要：本文回顾了这种调节的原理。批判性地讨论了血脑屏障HCO转运速率是慢还是快：倾向于与其他离子相当的慢转运速率。在代谢性酸中毒和碱中毒时，ISF中HCO浓度和pH的变化比血浆中小得多，而在呼吸性酸中毒时，pH和pH的变化相似。总结了这两个界面的关键异同点。
