Increasing the Permeability of the Blood-brain Barrier in Three Different Models in vivo
Increasing the Permeability of the Blood-brain Barrier in Three Different Models in vivo
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DOI：
10.1111/cns.12405
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发表时间：
2015-07-01
影响因子：
5.5
通讯作者：
Li, Ling
中科院分区：
文献类型：
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作者：
Liu, Wei-Ye;Wang, Zhi-Bin;Li, Ling
目的：血脑屏障（BBB）在中枢神经系统（CNS）的环境维持中起着重要作用。血脑屏障功能障碍可发生在所有中枢神经系统疾病的病理状态中，如缺血性中风、脑水肿或炎性疾病。然而，在体内不同血脑屏障破坏动物模型之间的比较仍需进一步研究。方法：采用MCAO模型、LPS模型和冷损伤模型，模拟临床情况。采用伊文思蓝染色法检测三种模型血脑屏障通透性。在三种不同的体内模型中比较了BBB的功能蛋白，包括claudin-5，VE-钙粘蛋白和小窝蛋白-1。结果如下：在三种模型中，随着伊文思蓝通透性增高，claudin-5和VE-cadherin的表达均降低，而caveolin-1的表达均升高。我们的研究表明，与LPS或冷损伤诱导的BBB通透性模型相比，MCAO诱导的小鼠BBB功能障碍相对稳定、可靠和温和，尽管操作时间通常较长且操作复杂。此外，我们的研究还发现，冷损伤的血脑屏障通透性增加的模型在局部脑组织中是严重的，而LPS处理的模型在整个脑组织中是轻微的。两种模型的体内操作简便、快速、稳定。结论：MCAO模型是研究血脑屏障通透性的最佳模型。
Aims: Blood-brain barrier (BBB) plays significant roles in the circumstance maintains for the central nervous system (CNS). The dysfunction of the BBB could occur in all pathological conditions of CNS diseases, such as ischemic stroke, cerebral edema, or inflammatory disorders. However, the comparisons among different animal models with a broken BBB in vivo are still need to be further studied. Methods: Here we used three different mice models in vivo, including MCAO induce, LPS treatment, and cold injury to mimic the situation in clinic. The permeability of BBB in three models was detected by perfusion of Evan's blue dye. The functional proteins of the BBB including claudin-5, VE-cadherin, and caveolin-1 were compared in three different models in vivo. Results: With the hyperpermeability of Evan's blue in the three models, both claudin-5 and VE-cadherin were decreased, while the expression of caveolin-1 was increased. Our study showed that BBB dysfunction induced by MCAO in mice was relatively stable, reliable, and moderate compared with LPS or cold injury-induced BBB permeability models, although the procedural time was generally long and operation complexity was hard. Moreover, our study also found that the model of the increased BBB permeability by cold injury was severe in the regional cerebral tissue and the model treated with LPS was mild in the global cerebral tissue. The operation of the two models in vivo was easy, quick, and stable. Conclusion: The MCAO model was the most suitable for studying the permeability of BBB among the three models in vivo.