Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.
Center for Neuroinflammation, Beijing TianTan Hospital, Beijing, 100070, China.
J Neuroinflammation. 2017 Dec 15;14(1):248. doi: 10.1186/s12974-017-1017-0.
Evidence suggests that brain infiltration of lymphocytes contributes to acute neural injury after cerebral ischemia. However, the spatio-temporal dynamics of brain-infiltrating lymphocytes during the late stage after cerebral ischemia remains unclear.
C57BL/6 (B6) mice were subjected to sham, photothrombosis, or 60-min transient middle cerebral artery occlusion (MCAO) procedures. Infarct volume, neurodeficits, production of reactive oxygen species (ROS) and inflammatory factors, brain-infiltrating lymphocytes, and their activation as well as pro-inflammatory cytokine IFN-γ production were assessed. Brain-infiltrating lymphocytes were also measured in tissue sections from post-mortem patients after ischemic stroke by immunostaining.
In mice subjected to transient MCAO or photothrombotic stroke, we found that lymphocyte infiltration persists in the ischemic brain until at least day 14 after surgery, during which brain infarct volume significantly diminished. These brain-infiltrating lymphocytes express activation marker CD69 and produce proinflammatory cytokines such as IFN-γ, accompanied with a sustained increase of reactive oxygen species (ROS) and inflammatory cytokines release in the brain. In addition, brain-infiltrating lymphocytes were observed in post-mortem brain sections from patients during the late stage of ischemic stroke.
Our results demonstrate that brain-infiltration of lymphocytes persists after the acute stage of cerebral ischemia, facilitating future advanced studies to reveal the precise role of lymphocytes during late stage of stroke.
有证据表明，淋巴细胞浸润脑实质会导致脑缺血后的急性神经损伤。然而，脑缺血后晚期脑内浸润淋巴细胞的时空动态仍不清楚。
C57BL/6（B6）小鼠接受假手术、光血栓形成或 60 分钟短暂性大脑中动脉闭塞（MCAO）处理。评估梗死体积、神经功能缺损、活性氧（ROS）和炎症因子的产生、脑内浸润的淋巴细胞及其激活以及促炎细胞因子 IFN-γ的产生。还通过免疫染色法在缺血性中风后患者的组织切片中测量脑内浸润的淋巴细胞。
在接受短暂性 MCAO 或光血栓性中风的小鼠中，我们发现淋巴细胞浸润在缺血性脑内持续存在，直到手术后至少 14 天，在此期间脑梗死体积显著减小。这些浸润的淋巴细胞表达激活标志物 CD69，并产生促炎细胞因子如 IFN-γ，同时伴有脑内 ROS 和炎症因子释放的持续增加。此外，在缺血性中风晚期的患者死后脑切片中观察到脑内浸润的淋巴细胞。
我们的研究结果表明，淋巴细胞浸润在脑缺血的急性期后持续存在，这为未来在中风晚期揭示淋巴细胞的确切作用的深入研究提供了依据。
