Leukocyte Invasion of the Brain After Experimental Intracerebral Hemorrhage in Mice

Leukocyte Invasion of the Brain After Experimental Intracerebral Hemorrhage in Mice
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DOI:
10.1161/strokeaha.114.005801
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发表时间:
2014-07-01
期刊:
影响因子:
8.3
通讯作者:
Veltkamp, Roland
Veltkamp, Roland
中科院分区:
医学1区
文献类型:
--
作者:
Mracsko, Eva;Javidi, Ehsan;Veltkamp, Roland

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背景和目的:脑出血后神经炎症过程可导致继发性神经元损伤。我们的目的是描述纹状体注射自体血或胶原酶后不同白细胞亚群脑迁移的时间过程。方法:采用自体血(20 μ L)或胶原酶(0.03 U)诱导C57Bl/6J小鼠脑出血。在冷冻切片上进行血肿体积测定。血红蛋白分光光度法测定血容量。从脑出血后1、3、5、14天的出血半球分离白细胞,进行白细胞标记染色,流式细胞术检测。利用CD45.1小鼠的异源血液注射来研究脑入侵白细胞的来源。结果:胶原酶注射液诱导的血肿体积较大,但血含量与普通注射剂相似。两种模型的出血性半球的脑白细胞浸润相似。从大脑中分离出来的白细胞大部分来自循环系统。CD4(+) T淋巴细胞是两种模型中主要的脑白细胞群。然而,与血液注射相比,胶原酶注射后的脑粒细胞计数更高。结论:两种脑出血模型中全身免疫细胞的脑浸润相似。入侵白细胞,特别是T细胞的病理生理影响需要进一步研究。
Background and Purpose-Neuroinflammatory processes contribute to secondary neuronal damage after intracerebral hemorrhage. We aimed to characterize the time course of brain immigration of different leukocyte subsets after striatal injection of either autologous blood or collagenase in mice.Methods-Intracerebral hemorrhage was induced by injection of either autologous blood (20 mu L) or collagenase (0.03 U) in C57Bl/6J mice. Hematoma volumetry was performed on cryosections. Blood volume was measured by hemoglobin spectrophotometry. Leukocytes were isolated from hemorrhagic hemisphere 1, 3, 5, and 14 days after intracerebral hemorrhage, stained for leukocyte markers, and measured by flow cytometry. Heterologous blood injection from CD45.1 mice was used to investigate the origin of brain-invading leukocytes.Results-Collagenase injection induced a larger hematoma volume but a similar blood content compared with blood injection. Cerebral leukocyte infiltration in the hemorrhagic hemisphere was similar in both models. The majority of leukocytes isolated from the brain originated from the circulation. CD4(+) T lymphocytes were the predominant brain leukocyte population in both models. However, cerebral granulocyte counts were higher after collagenase compared with blood injection.Conclusions-Brain infiltration of systemic immune cells is similar in both murine intracerebral hemorrhage models. The pathophysiological impact of invading leukocytes and, in particular, of T cells requires further investigation.