Differential permeability of the BBB in acute EAE: Enhanced transport of TNF-alpha
Differential permeability of the BBB in acute EAE: Enhanced transport of TNF-alpha
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DOI：
10.1152/ajpendo.1996.271.4.e636
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发表时间：
1996-10-01
影响因子：
5.1
通讯作者：
Kastin, AJ
中科院分区：
文献类型：
--
作者：
Pan, WH;Banks, WA;Kastin, AJ
实验性自身免疫性脑脊髓炎（EAE）中血脑屏障（BBB）的损害经常被归因于破坏，而没有太多考虑饱和转运过程。在患有EAE的小鼠中，我们研究了BBB对放射性标记的白蛋白和蔗糖的渗透性，这是BBB破坏的标志物，以及肿瘤坏死因子-α（TNF-α），这是一种通过饱和系统转运穿过BBB的细胞因子，被认为在EAE的发病机制中发挥作用。在急性病阶段，血脑屏障对所有三种物质的渗透增加，在腰椎中最大，并随着恢复而恢复正常。血脑屏障对蔗糖的渗透性变化大于对较大白蛋白的渗透性变化，这与血脑屏障的部分破坏一致。尽管TNF-α的大小与白蛋白相似，但TNF-α的渗透性增强与蔗糖相当。这种矛盾的高摄取TNF-α可以解释为增强其内源性饱和转运系统。因此，EAE期间BBB功能的变化超出了破坏范围，包括疾病过程中所涉及物质的饱和转运系统的变化。
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.