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首页> 外文期刊>Neuroscience: An International Journal under the Editorial Direction of IBRO >Focal cerebral ischemia/reperfusion injury in mice induces hematopoietic prostaglandin D synthase in microglia and macrophages.
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Focal cerebral ischemia/reperfusion injury in mice induces hematopoietic prostaglandin D synthase in microglia and macrophages.

机译：小鼠局灶性脑缺血/再灌注损伤在小胶质细胞和巨噬细胞中诱导造血前列腺素D合酶。

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摘要

Hematopoietic prostaglandin D synthase is a key enzyme in synthesis of prostaglandin D. Hematopoietic prostaglandin D synthase is expressed in microglia of the developing mouse brain. This study determined the serial changes and cellular localization of hematopoietic prostaglandin D synthase, and its role in cerebral ischemia/reperfusion injury using C57BL/6 mice (n=84) and bone marrow chimera mice (n=16). The latter mice were selected based on their expression of enhanced green fluorescent protein in bone marrow/blood-derived monocytes/macrophages. The middle cerebral artery was occluded for 60 min, followed by reperfusion. Hematopoietic prostaglandin D synthase expression was examined by immunohistochemistry and Western blotting. Hematopoietic prostaglandin D synthase-positive cells were mainly expressed in the peri-ischemic area at 12 h (P<0.05) and 24 h (P<0.001) after reperfusion, while they were mostly found in the transition area at 48-72 h postreperfusion (P<0.001). There was a significant increase in staining intensity as well as number of hematopoietic prostaglandin D synthase-positive cells in the ischemic core at 5-7 (P<0.001) days postreperfusion. Hematopoietic prostaglandin D synthase-positive cells also co-expressed ionized calcium-binding adapter molecule 1, a marker of microglia/macrophages, and cyclooxygenase-2, but not markers of neurons, oligodendrocytes and astrocytes. Until 72 h postreperfusion, many enhanced green fluorescent protein-positive cells were negative for hematopoietic prostaglandin D synthase, but the number of hematopoietic prostaglandin D synthase-enhanced green fluorescent protein coexpressing cells increased significantly at 5-7 days after reperfusion. Our results indicate that hematopoietic prostaglandin D synthase is mainly produced by endogenous microglia until 72 h after reperfusion, but at 7 days after reperfusion, it is also produced by migrating bone marrow/blood-derived macrophages in the ischemic brain tissue. We speculate that hematopoietic prostaglandinD synthase in the brain has different functions during early and late phases of ischemia.
机译：造血前列腺素D合酶是前列腺素D合成中的关键酶。造血前列腺素D合酶在发育中的小鼠脑的小胶质细胞中表达。这项研究确定了使用C57BL / 6小鼠（n = 84）和骨髓嵌合体小鼠（n = 16）造血前列腺素D合酶的系列变化和细胞定位，及其在脑缺血/再灌注损伤中的作用。根据它们在骨髓/血源性单核细胞/巨噬细胞中增强的绿色荧光蛋白的表达来选择后一种小鼠。将大脑中动脉闭塞60分钟，然后再灌注。通过免疫组织化学和Western印迹检查造血前列腺素D合酶的表达。造血前列腺素D合酶阳性细胞主要在再灌注后12 h（P <0.05）和24 h（P <0.001）的局部缺血区域表达，而多数在再灌注后48-72 h的过渡区表达（P ＜0.001）。在再灌注后5-7天（P <0.001），在缺血核心的染色强度以及造血前列腺素D合酶阳性细胞的数量显着增加。造血前列腺素D合酶阳性细胞也共表达了离子化的钙结合衔接子分子1，这是小胶质细胞/巨噬细胞和环氧合酶-2的标记，但不是神经元，少突胶质细胞和星形胶质细胞的标记。直到再灌注后72小时，许多增强的绿色荧光蛋白阳性细胞对造血前列腺素D合酶呈阴性，但在再灌注后5-7天，增强造血前列腺素D合酶的绿色荧光蛋白共表达细胞的数量显着增加。我们的结果表明，造血前列腺素D合酶主要由内源性小胶质细胞产生，直至再灌注后72 h，但在再灌注后7天，它也由骨髓/血源性巨噬细胞在缺血性脑组织中的迁移产生。我们推测在缺血的早期和晚期，大脑中的造血前列腺素D合酶具有不同的功能。

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