Infiltration and persistence of lymphocytes during late-stage cerebral ischemia in middle cerebral artery occlusion and photothrombotic stroke models.

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. The online version of this article (10.1186/s12974-017-1017-0) contains supplementary material, which is available to authorized users.

有证据表明，淋巴细胞的脑浸润在脑缺血后会导致急性神经损伤。然而，脑缺血后期脑浸润淋巴细胞的时空动态仍不清楚。 将C57BL/6（B6）小鼠分为假手术组、光化学血栓形成组或大脑中动脉闭塞（MCAO）60分钟短暂性缺血组。对梗死体积、神经功能缺损、活性氧（ROS）和炎症因子的产生、脑浸润淋巴细胞及其活化情况以及促炎细胞因子干扰素 -γ的产生进行评估。还通过免疫染色对缺血性脑卒中死后患者的组织切片中的脑浸润淋巴细胞进行检测。 在经历短暂性MCAO或光化学血栓性脑卒中的小鼠中，我们发现淋巴细胞浸润在缺血大脑中持续存在，至少持续到术后第14天，在此期间脑梗死体积显著减小。这些脑浸润淋巴细胞表达活化标志物CD69，并产生如干扰素 -γ等促炎细胞因子，同时伴有大脑中活性氧（ROS）的持续增加和炎症因子的释放。此外，在缺血性脑卒中后期患者的死后脑切片中也观察到了脑浸润淋巴细胞。 我们的研究结果表明，在脑缺血急性期之后淋巴细胞的脑浸润仍持续存在，这有助于未来进一步的研究揭示淋巴细胞在脑卒中后期的确切作用。 本文的网络版（10.1186/s12974 - 2017 - 1017 - 0）包含补充材料，授权用户可获取。