T lymphocytes infiltration promotes blood-brain barrier injury after experimental intracerebral hemorrhage
T lymphocytes infiltration promotes blood-brain barrier injury after experimental intracerebral hemorrhage
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DOI：
10.1016/j.brainres.2017.06.019
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发表时间：
2017-09
期刊：
影响因子：
2.9
通讯作者：
Xuan Zhang;Wei Liu;Jichao Yuan;Hai-tao Zhu;Yang Yang-Yang;Zexian Wen;Yaxing Chen;Lan Li;Jiangkai Lin;H. Feng
中科院分区：
文献类型：
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作者：
Xuan Zhang;Wei Liu;Jichao Yuan;Hai-tao Zhu;Yang Yang-Yang;Zexian Wen;Yaxing Chen;Lan Li;Jiangkai Lin;H. Feng
脑出血（ICH）后T淋巴细胞迁移入脑，促进脑炎症反应，从而加重神经元损伤。然而，脑出血后T淋巴细胞浸润与血脑屏障（BBB）损伤的关系尚不清楚。本研究采用免疫荧光和流式细胞术研究了C57 BL/6小鼠脑出血后浸润T淋巴细胞的时空分布，并通过伊文思蓝染料渗漏和紧密连接蛋白表达检测了伴随的血脑屏障通透性变化规律。此外，使用T淋巴细胞缺陷的裸鼠和T淋巴细胞减少的C57 BL/6小鼠用芬戈莫德处理以验证ICH后T淋巴细胞浸润与BBB渗漏的关系。在此，我们报道了出血半球的脑浸润性T淋巴细胞在ICH后第一天开始积聚，并在第五天达到峰值; BBB渗漏也在第五天达到峰值。此外，与C57 BL/6对照小鼠相比，T淋巴细胞缺陷裸鼠在ICH后显示出轻微的BBB渗漏。类似地，与媒介物对照相比，芬戈莫德治疗可显著减少T淋巴细胞浸润并促进BBB完整性。总之，我们的研究结果表明，抑制T淋巴细胞浸润可能是改善脑出血后血脑屏障完整性的一种新方法。
T lymphocytes migrate into the brain after intracerebral hemorrhage (ICH) and promote cerebral inflammation, thus exacerbating neuronal injury. However, the relationship between of T lymphocytes infiltration and blood-brain barrier (BBB) injury after ICH has not been clarified. In this study, we investigated the spatial-temporal distribution of infiltrating T lymphocytes after ICH in C57BL/6 mice by immunofluorescence and flow cytometry, and the accompanying change rules of BBB permeability were detected by Evans blue dye leakage and tight junction protein expression. Furthermore, T lymphocyte-deficient nude mice and T lymphocyte-decreased C57BL/6 mice treated with fingolimod were used to verify the relationship between T lymphocytes infiltration and BBB leakage after ICH. Here, we reported that brain-infiltrating T lymphocytes in the hemorrhagic hemisphere began to accumulate on the first day and peaked on the fifth day after ICH; BBB leakage also at peaked on the fifth day. Moreover, T lymphocyte-deficient nude mice showed minor BBB leakage after ICH compared with C57BL/6 control mice. Similarly, fingolimod treatment can significantly decrease T lymphocyte infiltration and promote BBB integrity compared with a vehicle control. Overall, our results suggested that suppression of T lymphocyte infiltration may be a novel way to improve BBB integrity after ICH.