Invasion of Peripheral Immune Cells into Brain Parenchyma after Cardiac Arrest and Resuscitation.
Invasion of Peripheral Immune Cells into Brain Parenchyma after Cardiac Arrest and Resuscitation.
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DOI：
10.14336/ad.2017.0926
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发表时间：
2018-06
影响因子：
7.4
通讯作者：
Dou H
中科院分区：
文献类型：
--
作者：
Zhang C;Brandon NR;Koper K;Tang P;Xu Y;Dou H
尽管长期以来人们一直怀疑全身免疫反应与中风后神经元损伤之间存在直接联系，但尚不清楚哪些免疫细胞发挥重要作用。仍然存在一个问题，即血脑屏障（BBB）是否在循环停止后短暂被破坏，从而允许外周免疫细胞进入脑实质。在这里，我们开发了一种临床相关的小鼠心脏骤停和复苏模型，以使用无创磁共振成像研究 BBB 完整性。通过免疫组织化学和流式细胞术检测大脑和外周免疫信号的变化。血池造影剂清除前后的 T1 加权差异图像的定量方差图显示，复苏后和再灌注一天后立即出现 BBB 破坏。海马 CA1 神经元损伤的时间分布与小胶质细胞激活的形态变化相关。心脏骤停和复苏三天后，大脑中的细胞毒性 T 细胞、CD11b+CD11c+ 树突状细胞、CD11b+CD45+hi 单核细胞和巨噬细胞显着增加，表明这些细胞在 BBB 破坏后直接浸润。重要的是，这些免疫细胞的变化与骨髓和血液中同一免疫细胞群的平行增加相结合。我们的结论是，初始再灌注阶段的神经血管破坏导致全身免疫细胞侵袭和随后的神经发病机制，影响心脏骤停和复苏后的长期结果。
Although a direct link has long been suspected between systemic immune responses and neuronal injuries after stroke, it is unclear which immune cells play an important role. A question remains as to whether the blood brain barrier (BBB) is transiently disrupted after circulatory arrest to allow peripheral immune cells to enter brain parenchyma. Here, we developed a clinically relevant cardiac arrest and resuscitation model in mice to investigate the BBB integrity using noninvasive magnetic resonance imaging. Changes in immune signals in the brain and periphery were assayed by immunohistochemistry and flow cytometry. Quantitative variance maps from T1-weighted difference images before and after blood-pool contrast clearance revealed BBB disruptions immediately after resuscitation and one day after reperfusion. Time profiles of hippocampal CA1 neuronal injuries correlated with the morphological changes of microglia activation. Cytotoxic T cells, CD11b+CD11c+ dendritic cells, and CD11b+CD45+hi monocytes and macrophages were significantly increased in the brain three days after cardiac arrest and resuscitation, suggesting direct infiltration of these cells following the BBB disruption. Importantly, these immune cell changes were coupled with a parallel increase in the same subset of immune cell populations in the bone marrow and blood. We conclude that neurovascular breakdown during the initial reperfusion phase contributes to the systemic immune cell invasion and subsequent neuropathogenesis affecting the long-term outcome after cardiac arrest and resuscitation.