The Spectrum of Systemic Immune Alterations After Murine Focal Ischemia Immunodepression Versus Immunomodulation
The Spectrum of Systemic Immune Alterations After Murine Focal Ischemia Immunodepression Versus Immunomodulation
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DOI：
10.1161/strokeaha.109.549618
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发表时间：
2009-08-01
期刊：
影响因子：
8.3
通讯作者：
Veltkamp, Roland
中科院分区：
文献类型：
--
作者：
Liesz, Arthur;Hagmann, Sebastien;Veltkamp, Roland
背景与目的：脑卒中后免疫过程的治疗性改变是当前脑卒中实验研究的一个关键目标。为了成功地转化为临床环境，实验研究必须考虑到不同中风对免疫系统的影响，包括对感染的易感性。在此，我们描述了3种缺血模型对全身免疫和微生物参数的影响。方法：在C57Bl/6小鼠（n = 235）中，通过远端凝血永久或短暂的腔内纤维阻塞大脑中动脉（MCAO） 30分钟或90分钟。分别在血液和淋巴器官中进行白细胞计数。流式细胞术检测淋巴细胞亚群和凋亡细胞。ELISA法检测血液细胞因子浓度。从血液和肺样本中培养微生物。结果：MCAO后24小时、3天和7天，仅大面积梗死引起白细胞减少，脾脏、淋巴结和胸腺淋巴细胞计数减少。相比之下，小梗死没有导致淋巴器官的差异血细胞计数或总细胞计数的显著变化。与轻度缺血相比，大范围损伤后脾淋巴细胞凋亡和血液细胞因子的产生显著增加。体温过低和体重减轻只发生在大面积梗死的小鼠身上，这些小鼠还患有肺炎和败血症。与梗死大小相反，梗死的位置和侧边不影响生理参数和免疫细胞的改变。结论：脑卒中模型的缺血性全身免疫调节和感染性并发症存在显著差异。脑卒中免疫调节疗法的转化研究必须考虑到这种异质性。（中风。2009;40:2849-2858）
Background and Purpose-Therapeutic modification of the postischemic immune processes is a key target of current experimental stroke research. For successful translation into the clinical setting, experimental studies must account for the impact of different strokes on the immune system including susceptibility to infection. Herein, we characterize the impact of 3 ischemia models on systemic immunological and microbiological parameters.Methods-In C57Bl/6 mice (n = 235), the middle cerebral artery was occluded (MCAO) either permanently by distal coagulation or transiently by an intraluminal filament for 30 minutes or 90 minutes. Differential leukocyte counts were performed in blood and lymphatic organs. Lymphocyte subpopulations and apoptotic cells were characterized by flow cytometry. Blood cytokine concentrations were measured by ELISA. Microbiological cultures were grown from blood and lung samples.Results-Only extensive infarcts induced leukopenia 24 hours, 3 days and 7 days after MCAO and decreased lymphocyte counts in spleen, lymph nodes and thymus. In contrast, small infarcts led to no significant changes in differential blood count or reduction of overall cell counts in lymphatic organs. Splenic lymphocyte apoptosis and blood cytokine production was significantly increased after extensive lesions compared to mild ischemia. Hypothermia and weight loss occurred only in mice with large infarcts which also suffered from pneumonia and sepsis. In contrast to infarct size, location and side of the infarct did not affect physiological parameters and immune cell alterations.Conclusions-Postischemic systemic immunomodulation and infectious complications differ substantially among stroke models. Translational studies of immunomodulatory therapies for stroke must account for this heterogeneity. (Stroke. 2009; 40: 2849-2858.)