From the Department of Neurology, University Heidelberg, Heidelberg, Germany (E.M., E.J., S.-Y.N., A.K., A.L.); Institute for Stroke and Dementia Research, University Hospital Munich, Munich, Germany (A.L.); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (A.L.); and Division of Brain Sciences, Imperial College, London, United Kingdom (R.V.).
Stroke. 2014 Jul;45(7):2107-14. doi: 10.1161/STROKEAHA.114.005801. Epub 2014 Jun 10.
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.
Intracerebral hemorrhage was induced by injection of either autologous blood (20 μL) 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.
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.
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.
神经炎症过程导致脑出血后的继发性神经元损伤。我们旨在描述在小鼠纹状体注射自体血或胶原酶后不同白细胞亚群向脑内迁移的时间过程。
通过向 C57Bl/6J 小鼠注射自体血(20 μL)或胶原酶(0.03 U)来诱导脑出血。在冷冻切片上进行血肿体积测定。通过血红蛋白分光光度法测量血容量。在脑出血后 1、3、5 和 14 天,从出血半球分离白细胞,用白细胞标志物染色,通过流式细胞术进行测量。使用来自 CD45.1 小鼠的异源血注射来研究侵入脑内的白细胞的来源。
胶原酶注射引起的血肿体积大于但与血注射相比血液含量相似。两种模型中出血半球的脑白细胞浸润相似。从脑中分离出的白细胞主要来源于循环。在两种模型中,CD4+T 淋巴细胞都是主要的脑白细胞群体。然而,与血注射相比,胶原酶后脑粒细胞计数更高。
在两种小鼠脑出血模型中,全身免疫细胞向脑内浸润相似。侵入的白细胞,特别是 T 细胞的病理生理影响需要进一步研究。