Partial MHC Constructs Treat Thromboembolic Ischemic Stroke Characterized by Early Immune Expansion.
Partial MHC Constructs Treat Thromboembolic Ischemic Stroke Characterized by Early Immune Expansion.
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DOI：
10.1007/s12975-015-0436-4
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发表时间：
2016-02
影响因子：
6.9
通讯作者：
Offner H
中科院分区：
文献类型：
--
作者：
Dotson AL;Chen Y;Zhu W;Libal N;Alkayed NJ;Offner H
炎症和血栓形成密切相关，炎症导致血栓栓塞和卒中结局。血栓栓塞是缺血性中风的常见原因，然而最常用的实验性中风的闭塞小鼠模型不能有效地复制血栓栓塞。我们的研究小组最近描述了一种新的血栓栓塞性中风小鼠模型，该模型成功地阻塞了大脑中动脉，具有高重现性。在目前的研究中，我们在临床相关的血栓栓塞性中风小鼠模型中描述了外周和局部免疫结果以及对免疫治疗的缺血反应。在血栓栓塞性中风后24小时收获脑和脾组织，并通过流式细胞术对细胞进行免疫表型分析。我们观察到中性粒细胞和早期活化的T细胞在脾脏中的显着增加，中性粒细胞和活化的单核细胞/小胶质细胞在缺血性皮质血栓栓塞性中风后的增加。此外，如先前对于短暂性MCAO模型所示，用部分MHC构建体治疗血栓栓塞性中风显著降低缺血性损伤，表明这种基于免疫的治疗在血栓栓塞模型中具有等效效果，其更好地模拟了人类中风的病理生理学。
Inflammation and thrombosis are tightly linked, with inflammation contributing to thromboembolism and to stroke outcome. Thromboembolism is a frequent cause of ischemic stroke, yet the most used occlusion mouse models of experimental stroke do not effectively replicate thromboembolism. Our group recently described a novel thromboembolic mouse model of stroke that successfully occludes the middle cerebral artery with high reproducibility. In the current study, we characterize the peripheral and local immune outcomes as well as the ischemic response to immune therapy in a clinically relevant mouse model of thromboembolic stroke. Brain and spleen tissues were harvested 24 hours after thromboembolic stroke and cells immunophenotyped by flow cytometry. We observed a significant increase in neutrophils and early activated T cells in the spleen and an increase in neutrophils and activated monocytes/microglia in the ischemic cortex after thromboembolic stroke. Moreover, as was shown previously for transient MCAO models, treatment of thromboembolic stroke with partial MHC constructs significantly reduced ischemic damage indicating an equivalent effect of this immune-based therapy in the thromboembolic model that better mimics the pathophysiology of human stroke.