Burns Impair Blood-Brain Barrier and Mesenchymal Stem Cells Can Reverse the Process in Mice.
Burns Impair Blood-Brain Barrier and Mesenchymal Stem Cells Can Reverse the Process in Mice.
复制标题
烧伤损害血脑屏障，间充质干细胞可以逆转小鼠的这一过程
DOI：
10.3389/fimmu.2020.578879
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发表时间：
2020
影响因子：
7.3
通讯作者：
Fu X
中科院分区：
文献类型：
--
作者：
Yang J;Ma K;Zhang C;Liu Y;Liang F;Hu W;Bian X;Yang S;Fu X
在许多烧伤患者中观察到神经系统综合症，这增加了社会和家庭的经济负担。最近的研究表明，血脑屏障（BBB）功能障碍是在周围创伤性疾病（例如手术和烧伤）中诱发这些中枢神经系统（CNS）综合征的关键因素。然而，烧伤对 BBB 的影响及其潜在机制在很大程度上仍有待确定。本研究旨在探讨烧伤对血脑屏障的影响以及具有强大抗炎和修复能力的脐带间充质干细胞（UC-MSCs）保护血脑屏障完整性的潜力。使用葡聚糖示踪剂（免疫组织化学成像和分光光度定量）评估 BBB 通透性，并通过酶联免疫吸附测定测量血液和脑中的蛋白质印迹、白细胞介素 (IL)-6 和 IL-1β 水平。此外，使用透射电子显微镜 (TEM) 检测 BBB 中的跨细胞囊泡转运（转胞吞作用）。我们发现烧伤增加了小鼠 BBB 对 10-kDa 和 70-kDa 葡聚糖的通透性。烧伤后外周血和中枢神经系统中IL-6和IL-1β水平升高。此外，烧伤降低了紧密连接蛋白（TJ）的水平，包括claudin-5、occludin和ZO-1，这表明由于细胞旁途径导致BBB通透性增加。此外，烧伤后囊泡密度增加表明脑微血管内皮细胞的转胞吞作用增加。最后，在烧伤后 1 小时施用 UC-MSC 可有效逆转这些不利影响并保护 BBB 的完整性。这些结果表明，烧伤通过细胞旁途径和转胞吞作用增加BBB通透性，其潜在机制可能是通过增加IL-6和IL-1β水平并降低Mfsd2a水平，而UC-MSCs的适当治疗可以逆转这些影响并保护烧伤后BBB的完整性。
Neurological syndromes are observed in numerous patients who suffer burns, which add to the economic burden of societies and families. Recent studies have implied that blood–brain barrier (BBB) dysfunction is the key factor that induces these central nervous system (CNS) syndromes in peripheral traumatic disease, e.g., surgery and burns. However, the effect of burns on BBB and the underlying mechanism remains, largely, to be determined. The present study aimed to investigate the effect of burns on BBB and the potential of umbilical cord-derived mesenchymal stem cells (UC-MSCs), which have strong anti-inflammatory and repairing ability, to protect the integrity of BBB. BBB permeability was evaluated using dextran tracer (immunohistochemistry imaging and spectrophotometric quantification) and western blot, interleukin (IL)-6, and IL-1β levels in blood and brain were measured by enzyme-linked immunosorbent assay. Furthermore, transmission electron microscopy (TEM) was used to detect transcellular vesicular transport (transcytosis) in BBB. We found that burns increased mouse BBB permeability to both 10-kDa and 70-kDa dextran. IL-6 and IL-1β levels increased in peripheral blood and CNS after burns. In addition, burns decreased the level of tight junction proteins (TJs), including claudin-5, occludin, and ZO-1, which indicated increased BBB permeability due to paracellular pathway. Moreover, increased vesicular density after burns suggested increased transcytosis in brain microvascular endothelial cells. Finally, administering UC-MSCs at 1 h after burns effectively reversed these adverse effects and protected the integrity of BBB. These results suggest that burns increase BBB permeability through both paracellular pathway and transcytosis, the potential mechanism of which might be through increasing IL-6 and IL-1β levels and decreasing Mfsd2a level, and appropriate treatment with UC-MSCs can reverse these effects and protect the integrity of BBB after burns.