Farrell C L, Shivers R R
Acta Neuropathol. 1984;63(3):179-89. doi: 10.1007/BF00685243.
Osmotic opening of the blood-brain barrier had no effect on the structure of the interendothelial tight junctions located within approximately 9 micron 2 of brain capillary endothelial plasma membrane (junction-containing) examined in this study. These tight junctions restrict the passive diffusion between the blood and the brain and constitute the anatomic basis of the blood-brain barrier. Increased permeability of the blood-brain barrier in the cerebral cortex of the right hemisphere of rats, induced by an infusion of a hypertonic solution of arabinose and monitored with the protein tracer horseradish peroxidase (HRP), was evidenced by the extravasation of the tracer into the extracellular compartment of the brain. Freeze-fracture analysis of the capillaries from the same tissue revealed no alterations in the intramembrane components of the endothelial tight junctions. The junctions, which consist of 8-12 highly anastomosed parallel ridges situated on the PF fracture face of the endothelial plasmalemma, showed no loss of ridge continuity or intra-ridge connections, and were identical to zonulae occludentes from control capillaries. Consistent labeling of numerous vesiculo-tubular elements by HRP in the endothelia of experimental tissue and the three-dimensional nature of these elements observed in platinum replicas support the interpretation that these structures represent transendothelial conduits which are continuous with the luminal and abluminal surfaces of the endothelial cells. Absence of similar structures in control endothelia is taken as evidence that their presence in experimental tissues is a direct response to the osmotic insult. It was concluded, therefore, that during osmotic opening of the blood-brain barrier passage of HRP across the endothelium of brain capillaries is not by an inter-endothelial route due to disruption of tight junctions but rather by a transendothelial route due to amplified vesicular activity.
血脑屏障的渗透性开放对本研究中所检测的脑毛细血管内皮细胞质膜（含连接）约9平方微米范围内的内皮间紧密连接结构没有影响。这些紧密连接限制了血液与脑之间的被动扩散，构成了血脑屏障的解剖学基础。通过注入阿拉伯糖高渗溶液诱导大鼠右半球大脑皮质血脑屏障通透性增加，并用蛋白质示踪剂辣根过氧化物酶（HRP）进行监测，示踪剂外渗到脑的细胞外间隙证明了通透性增加。对同一组织的毛细血管进行冷冻断裂分析，结果显示内皮紧密连接的膜内成分没有改变。这些连接由位于内皮细胞质膜PF断裂面上的8 - 12条高度吻合的平行嵴组成，嵴的连续性或嵴内连接没有丧失，与对照毛细血管的紧密连接相同。在实验组织的内皮细胞中HRP对许多囊泡 - 管状结构的持续标记以及在铂复制品中观察到的这些结构的三维性质支持了这样的解释，即这些结构代表与内皮细胞腔面和腔外表面连续的跨内皮通道。对照内皮细胞中没有类似结构，这被视为实验组织中它们的存在是对渗透性损伤的直接反应的证据。因此得出结论，在血脑屏障渗透性开放期间，HRP穿过脑毛细血管内皮的途径不是由于紧密连接破坏通过内皮间途径，而是由于囊泡活性增强通过跨内皮途径。
