Zhang Xuan, Liu Wei, Yuan Jichao, Zhu Haitao, Yang Yang, Wen Zexian, Chen Yaxing, Li Lan, Lin Jiangkai, Feng Hua
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Brain Res. 2017 Sep 1;1670:96-105. doi: 10.1016/j.brainres.2017.06.019. Epub 2017 Jun 17.
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.
脑出血（ICH）后T淋巴细胞迁移至脑内，促进脑部炎症，从而加剧神经元损伤。然而，脑出血后T淋巴细胞浸润与血脑屏障（BBB）损伤之间的关系尚未阐明。在本研究中，我们通过免疫荧光和流式细胞术研究了C57BL/6小鼠脑出血后浸润性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血脑屏障通透性的伴随变化规律。此外，使用T淋巴细胞缺陷的裸鼠和用芬戈莫德治疗的T淋巴细胞减少的C57BL/6小鼠来验证脑出血后T淋巴细胞浸润与血脑屏障渗漏之间的关系。在此，我们报告出血半球的脑浸润性T淋巴细胞在脑出血后第1天开始聚集，并在第5天达到峰值；血脑屏障渗漏也在第5天达到峰值。此外，与C57BL/6对照小鼠相比，T淋巴细胞缺陷的裸鼠在脑出血后血脑屏障渗漏较轻。同样，与载体对照相比，芬戈莫德治疗可显著减少T淋巴细胞浸润并促进血脑屏障完整性。总体而言，我们的结果表明抑制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。
