Pan W, Banks W A, Kennedy M K, Gutierrez E G, Kastin A J
Department of Neuroscience, Tulane University School of Medicine, New Orleans, Louisiana, USA.
Am J Physiol. 1996 Oct;271(4 Pt 1):E636-42. doi: 10.1152/ajpendo.1996.271.4.E636.
Impairment of the blood-brain barrier (BBB) in experimental autoimmune encephalomyelitis (EAE) has been frequently attributed to disruption, without much consideration of saturable transport processes. In mice with EAE, we studied the permeability of the BBB to radioactively labeled albumin and sucrose, markers of BBB disruption, and tumor necrosis factor-alpha (TNF-alpha), a cytokine transported across the BBB by a saturable system and thought to play a role in the pathogenesis of EAE. Permeation of the BBB was increased to all three substances during the acutely ill stage, was greatest in the lumbar spine, and returned to normal with recovery. The change in BBB permeability to sucrose was greater than to the larger albumin and is consistent with a partial disruption of the BBB. The enhanced permeability to TNF-alpha was comparable to that for sucrose, even though TNF-alpha is similar in size to albumin. This paradoxically high uptake of TNF-alpha could be explained by an enhancement of its endogenous saturable transport system. Thus the changes in BBB function during EAE extend beyond disruption to include changes in the saturable transport systems for substances involved in the disease process.
实验性自身免疫性脑脊髓炎（EAE）中血脑屏障（BBB）的损伤常常被归因于其破坏，而很少考虑可饱和转运过程。在患有EAE的小鼠中，我们研究了血脑屏障对放射性标记的白蛋白和蔗糖（血脑屏障破坏的标志物）以及肿瘤坏死因子-α（TNF-α，一种通过可饱和系统跨血脑屏障转运且被认为在EAE发病机制中起作用的细胞因子）的通透性。在急性发病阶段，血脑屏障对这三种物质的通透性均增加，在腰椎处最为明显，并随着恢复而恢复正常。血脑屏障对蔗糖的通透性变化大于对更大的白蛋白的变化，这与血脑屏障的部分破坏一致。对TNF-α的通透性增强与对蔗糖的相当，尽管TNF-α的大小与白蛋白相似。TNF-α这种反常的高摄取可以通过其内源性可饱和转运系统的增强来解释。因此，EAE期间血脑屏障功能的变化不仅包括破坏，还包括疾病过程中相关物质的可饱和转运系统的变化。
