Møllgård K, Saunders N R
Neuropathol Appl Neurobiol. 1986 Jul-Aug;12(4):337-58. doi: 10.1111/j.1365-2990.1986.tb00146.x.
The commonly held belief that the fetal blood-brain and blood-CSF barriers are immature is reviewed. Results obtained from carefully conducted experiments with horseradish peroxidase and optimal freeze-fracturing suggest that the chick, rat and monkey brain barrier systems to proteins are tight from the earliest stages of development. Previous studies are reviewed in the light of new information on retrograde axonal transport, circumventricular organs, the proper use of horseradish peroxidase, freeze-fracturing, immunocytochemistry and plasma protein gene expression in the developing human brain. Original data on the development of human brain barrier systems are included. Tight junctions between cerebral endothelial and choroid plexus epithelial cells form the morphological basis for these systems. CSF in the fetus contains a remarkably high concentration of protein in contrast to adult CSF which is characterized by a very low protein concentration. This has previously been interpreted as due to immaturity of barriers in the fetal brain. Tight junctions between cerebral endothelial cells and between choroid plexus epithelial cells have been investigated in human embryos and fetuses by freeze fracture and thin section electron microscopy. As soon as the choroid plexus and the brain capillaries differentiated they exhibited well formed tight junctions. These junctions were very complex at early stages of development. A new barrier consisting of 'strap junctions' was found in the developing germinal matrix. The very high concentration of protein in early human fetal CSF cannot be accounted for by a lack of tight junctions in the developing brain barrier systems. Some transfer of proteins from blood to CSF, possibly via an intracellular route, has been demonstrated in immature experimental animals, but it seems that an important contribution to CSF proteins in the fetus may be synthesis by the developing brain and choroid plexuses with subsequent release into the CSF.
本文回顾了一种普遍观点，即胎儿的血脑屏障和血脑脊液屏障不成熟。通过用辣根过氧化物酶进行的精心实验以及最佳冷冻断裂技术获得的结果表明，鸡、大鼠和猴的大脑对蛋白质的屏障系统从发育的最早阶段就很紧密。根据有关逆行轴突运输、室周器官、辣根过氧化物酶的正确使用、冷冻断裂、免疫细胞化学以及发育中的人类大脑中血浆蛋白基因表达的新信息，对先前的研究进行了回顾。其中包括关于人类大脑屏障系统发育的原始数据。脑内皮细胞和脉络丛上皮细胞之间的紧密连接构成了这些系统的形态学基础。与蛋白质浓度非常低的成体脑脊液相比，胎儿脑脊液中蛋白质浓度极高。此前这被解释为由于胎儿脑屏障不成熟所致。通过冷冻断裂和超薄切片电子显微镜对人类胚胎和胎儿的脑内皮细胞之间以及脉络丛上皮细胞之间的紧密连接进行了研究。一旦脉络丛和脑毛细血管分化，它们就表现出形成良好的紧密连接。这些连接在发育早期非常复杂。在发育中的生发基质中发现了一种由“带状连接”组成的新屏障。发育中的大脑屏障系统中缺乏紧密连接并不能解释人类胎儿早期脑脊液中蛋白质的极高浓度。在未成熟实验动物中已证实蛋白质可能通过细胞内途径从血液向脑脊液有一些转运，但似乎对胎儿脑脊液蛋白质的重要贡献可能是由发育中的大脑和脉络丛合成并随后释放到脑脊液中。
