Temporal and Spatial Dynamics of Cerebral Immune Cell Accumulation in Stroke
Temporal and Spatial Dynamics of Cerebral Immune Cell Accumulation in Stroke
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DOI：
10.1161/strokeaha.108.534503
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发表时间：
2009-05-01
期刊：
影响因子：
8.3
通讯作者：
Magnus, Tim
中科院分区：
文献类型：
--
作者：
Gelderblom, Mathias;Leypoldt, Frank;Magnus, Tim
背景与目的——在西方世界，缺血性脑卒中导致显著的发病率和死亡率。早期再灌注策略仍然是首选治疗方法，但可引发并增强炎症反应，导致继发性脑损伤。对缺血后炎症的了解非常有限。本研究的目的是确定在小鼠脑缺血再灌注损伤模型中免疫细胞群的时空浸润及其活化模式。
方法——在C57/BL6小鼠中诱导大脑中动脉短暂闭塞1小时，随后再灌注12小时至7天。采用免疫组织化学和流式细胞术对浸润的免疫细胞亚群进行定量。
结果——小胶质细胞的聚集以及巨噬细胞、淋巴细胞和树突状细胞（DC）对缺血半球的浸润先于中性粒细胞的流入。发现DC增加了20倍，并且在浸润细胞中占相当大的比例。DC的主要组织相容性复合体II显著上调，并且主要组织相容性复合体II高表达的DC比假手术组丰富100倍。在DC和小胶质细胞中观察到共刺激分子CD80的上调，但在主要组织相容性复合体II高表达的DC中没有进一步增加。未观察到淋巴细胞活化。此外，调节性免疫细胞（自然杀伤T细胞、CD4⁻/CD8⁻T淋巴细胞）在缺血半球聚集。
结论——本研究详细分析了啮齿动物脑卒中模型中免疫细胞聚集的时间动态。抗原呈递细胞的特殊活化模式及其大量增加与调节性细胞在时间上的关联可能为脑卒中后的免疫调节提供更多的见解。（《卒中》2009年；40卷：1849 - 1857页）
Background and Purpose-Ischemic stroke leads to significant morbidity and mortality in the Western world. Early reperfusion strategies remain the treatment of choice but can initiate and augment an inflammatory response causing secondary brain damage. The understanding of postischemic inflammation is very limited. The objectives of this study were to define the temporal and spatial infiltration of immune cell populations and their activation patterns in a murine cerebral ischemia-reperfusion injury model.Methods-Transient middle cerebral artery occlusion was induced for 1 hour followed by 12-hour to 7-day reperfusion in C57/BL6 mice. Immunohistochemistry and flow cytometry were used to quantify the infiltrating immune cell subsets.Results-Accumulation of microglia and infiltration of the ischemic hemisphere by macrophages, lymphocytes, and dendritic cells (DCs) preceded the neutrophilic influx. DCs were found to increase 20-fold and constituted a substantial proportion of infiltrating cells. DCs exhibited a significant upregulation of major histocompatibility complex II and major histocompatibility complex II high-expressing DCs were found 100 times more abundant than in sham conditions. Upregulation of the costimulatory molecule CD80 was observed in DCs and microglial cells but did not further increase in major histocompatibility complex II high-expressing DCs. No lymphocyte activation was observed. Additionally, regulatory immune cells (natural killer T-cells, CD4(-)/CD8(-)T lymphocytes) cumulated in the ischemic hemisphere.Conclusion-This study provides a detailed analysis of the temporal dynamics of immune cell accumulation in a rodent stroke model. The peculiar activation pattern and massive increase of antigen-presenting cells in temporal conjunction with regulatory cells might provide additional insight into poststroke immune regulation. (Stroke. 2009; 40:1849-1857.)