Microglia and macrophages differentially modulate cell death after brain injury caused by oxygen-glucose deprivation in organotypic brain slices.
Microglia and macrophages differentially modulate cell death after brain injury caused by oxygen-glucose deprivation in organotypic brain slices.
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小胶质细胞和巨噬细胞在器官脑切片中由氧葡萄糖剥夺引起的脑损伤后调节细胞死亡。
DOI：
10.1002/glia.22478
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发表时间：
2013-05
期刊：
影响因子：
6.2
通讯作者：
Allan, Stuart M.
中科院分区：
文献类型：
--
作者：
Girard, Sylvie;Brough, David;Lopez-Castejon, Gloria;Giles, James;Rothwell, Nancy J.;Allan, Stuart M.
巨噬细胞可呈现多种表型，这一过程称为极化，对形成针对损伤的炎症反应至关重要。目前尚不清楚小胶质细胞（一种驻留在脑内的巨噬细胞群体）是否以类似方式极化，以及特定的小胶质细胞表型是否会调节脑损伤后的细胞死亡。在本研究中，我们发现BV2小胶质细胞和小鼠骨髓来源的巨噬细胞（BMDMs）在体外经脂多糖（LPS，诱导M1型）或白细胞介素 - 4（IL - 4，诱导M2型）处理后能够呈现不同表型，但将它们加入小鼠海马脑片后对细胞死亡的调节作用不同。BMDMs加入对照脑片时会诱导细胞死亡，并且在与氧 - 糖剥夺（OGD）联合时会加剧损伤，且这种作用与其表型无关。相比之下，空白对照和M2型BV2小胶质细胞对OGD诱导的死亡具有保护作用。用IL - 4直接处理脑片（不添加细胞）对OGD具有保护作用，并在脑片中诱导出M2表型。在体内，向小鼠脑内注射LPS或IL - 4诱导出的小胶质细胞表型与在脑片和培养细胞中观察到的表型相似。大脑中动脉闭塞诱导损伤后，小胶质细胞未呈现经典的M1/M2表型，这表明诱导出了另一种调节性表型亚型。本研究强调了巨噬细胞和小胶质细胞在应对脑损伤时的功能差异，其结果存在根本不同，即便这两种细胞群体都能够呈现M1或M2表型。这些数据表明，损伤后从外周浸润到脑内的巨噬细胞可能具有细胞毒性，且与表型无关，而小胶质细胞可能具有保护作用。
Macrophage can adopt several phenotypes, process call polarization, which is crucial for shaping inflammatory responses to injury. It is not known if microglia, a resident brain macrophage population, polarizes in a similar way, and whether specific microglial phenotypes modulate cell death in response to brain injury. In this study, we show that both BV2-microglia and mouse bone marrow derived macrophages (BMDMs) were able to adopt different phenotypes after LPS (M1) or IL-4 (M2) treatment in vitro, but regulated cell death differently when added to mouse organotypic hippocampal brain slices. BMDMs induced cell death when added to control slices and exacerbated damage when combined with oxygen–glucose deprivation (OGD), independently of their phenotype. In contrast, vehicle- and M2-BV2-microglia were protective against OGD-induced death. Direct treatment of brain slices with IL-4 (without cell addition) was protective against OGD and induced an M2 phenotype in the slice. In vivo, intracerebral injection of LPS or IL-4 in mice induced microglial phenotypes similar to the phenotypes observed in brain slices and in cultured cells. After injury induced by middle cerebral artery occlusion, microglial cells did not adopt classical M1/M2 phenotypes, suggesting that another subtype of regulatory phenotype was induced. This study highlights functional differences between macrophages and microglia, in response to brain injury with fundamentally different outcomes, even if both populations were able to adopt M1 or M2 phenotypes. These data suggest that macrophages infiltrating the brain from the periphery after an injury may be cytotoxic, independently of their phenotype, while microglia may be protective.
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DOI：
10.1523/jneurosci.2102-11.2011
发表时间：
2011-09-07
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Faustino JV;Wang X;Johnson CE;Klibanov A;Derugin N;Wendland MF;Vexler ZS
通讯作者：
Vexler ZS
影响因子：
6.3
作者：
Denes, Adam;Vidyasagar, Rishma;Allan, Stuart M.
通讯作者：
Allan, Stuart M.
影响因子：
6.2
作者：
Durafourt, Bryce A.;Moore, Craig S.;Antel, Jack P.
通讯作者：
Antel, Jack P.
影响因子：
4.7
作者：
Pinteaux, E;Parker, LC;Luheshi, GN
通讯作者：
Luheshi, GN
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG