Comparison of the detrimental features of microglia and infiltrated macrophages in traumatic brain injury: A study using a hypnotic bromovalerylurea
Comparison of the detrimental features of microglia and infiltrated macrophages in traumatic brain injury: A study using a hypnotic bromovalerylurea
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DOI：
10.1002/glia.23469
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发表时间：
2018-10-01
期刊：
影响因子：
6.2
通讯作者：
Tanaka, Junya
中科院分区：
文献类型：
--
作者：
Abe, Naoki;Choudhury, Mohammed E.;Tanaka, Junya
受伤或患病大脑中的小胶质细胞和血源性巨噬细胞很难区分，因为它们有许多共同的特征。然而，最近小胶质细胞特异性标记的鉴定和流式细胞术的使用使得区分这些类型的细胞变得容易。在这项研究中，我们分析了大鼠创伤性脑损伤（TBI）模型中血源性巨噬细胞、活化和静息小胶质细胞的特征。8-羟基-2 '-脱氧鸟苷（8-OHdG）的存在表明TBI损伤中的巨噬细胞和神经元中存在氧化损伤。在粒细胞和巨噬细胞中明显观察到线粒体活性氧（ROS）的产生，但在活化或静息的小胶质细胞中没有观察到。二氢乙锭染色支持小胶质细胞不是TBI病变中ROS的主要来源。此外，巨噬细胞表达NADPH氧化酶2、白细胞介素-1 β（IL-1 β）和CD 68的水平高于小胶质细胞。相比之下，小胶质细胞表达转化生长因子β 1（TGF β 1）、白细胞介素-6（IL-6）和肿瘤坏死因子α的水平高于巨噬细胞。一种催眠药，溴戊脲（BU），具有抗炎作用，减少糖酵解和线粒体耗氧量。BU管理抑制趋化因子CCL 2的表达，单核细胞/巨噬细胞的积累，8-OHdG的产生，线粒体ROS的产生，和促炎细胞因子的表达，并显着改善TBI模型的结果。然而，BU不抑制小胶质细胞活化或TGF β 1和胰岛素样生长因子1（IGF-1）的表达。这些结果表明，巨噬细胞是TBI病变的主要加重细胞类型，特别是在急性期。活化的小胶质细胞甚至可能发挥有利的作用。巨噬细胞能量代谢的降低和损伤组织中CCL 2表达的抑制可能导致TBI的改善。
Microglia and blood-borne macrophages in injured or diseased brains are difficult to distinguish because they share many common characteristics. However, the identification of microglia-specific markers and the use of flow cytometry have recently made it easy to discriminate these types of cells. In this study, we analyzed the features of blood-borne macrophages, and activated and resting microglia in a rat traumatic brain injury (TBI) model. Oxidative injury was indicated in macrophages and neurons in TBI lesions by the presence of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Generation of mitochondrial reactive oxygen species (ROS) was markedly observed in granulocytes and macrophages, but not in activated or resting microglia. Dihydroethidium staining supported microglia not being the major source of ROS in TBI lesions. Furthermore, macrophages expressed NADPH oxidase 2, interleukin-1 beta (IL-1 beta), and CD68 at higher levels than microglia. In contrast, microglia expressed transforming growth factor beta 1 (TGF beta 1), interleukin-6 (IL-6), and tumor necrosis factor alpha at higher levels than macrophages. A hypnotic, bromovalerylurea (BU), which has anti-inflammatory effects, reduced both glycolysis and mitochondrial oxygen consumption. BU administration inhibited chemokine CCL2 expression, accumulation of monocytes/macrophages, 8-OHdG generation, mitochondrial ROS generation, and proinflammatory cytokine expression, and markedly ameliorated the outcome of the TBI model. Yet, BU did not inhibit microglial activation or expression of TGF beta 1 and insulin-like growth factor 1 (IGF-1). These results indicate that macrophages are the major aggravating cell type in TBI lesions, in particular during the acute phase. Activated microglia may even play favorable roles. Reduction of cellular energy metabolism in macrophages and suppression of CCL2 expression in injured tissue may lead to amelioration of TBI.