Effects of an Inhibitor of Monocyte Recruitment on Recovery from Traumatic Brain Injury in Mice Treated with Granulocyte Colony-Stimulating Factor.
Effects of an Inhibitor of Monocyte Recruitment on Recovery from Traumatic Brain Injury in Mice Treated with Granulocyte Colony-Stimulating Factor.
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DOI：
10.3390/ijms18071418
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发表时间：
2017-07-02
影响因子：
5.6
通讯作者：
Sanchez-Ramos J
中科院分区：
文献类型：
--
作者：
Song S;Kong X;Acosta S;Sava V;Borlongan CV;Sanchez-Ramos J
据报道，在啮齿类动物模型中，给予造血生长因子粒细胞集落刺激因子（G-CSF）可增强受控皮质撞击（CCI）的恢复。G-CSF在外周（刺激造血）和脑中发挥作用，在脑中作为神经营养因子，促进神经元存活并刺激海马中的神经干细胞/祖细胞增殖。为了区分G-CSF的直接CNS作用与其外周作用，设计实验以阻断外周单核细胞向CCI产生的损伤部位的募集。CCI后，在先前移植了GFP表达（GFP+）造血干细胞-祖细胞的嵌合小鼠中，将选择性C-C基序受体2（CCR 2）拮抗剂（RS 504303）与G-CSF联合给药3天。结果如下：该药物显著损害GFP+骨髓源性细胞向额叶皮质和纹状体的浸润，而不妨碍行为测试（桡臂水迷宫（RAWM））中的恢复表现和海马神经发生。单独给予CCR 2拮抗剂，而不加G-CSF，可有效促进RAWM的恢复。这些结果支持了这样的假设，即G-CSF对神经细胞的直接作用，独立于其造血作用，是CCI恢复增强的主要原因。此外，本研究证实了CCR 2及其配体单核细胞趋化蛋白-1（MCP-1）在介导CCI后炎症反应中的重要性。
Administration of the hematopoietic growth factor granulocyte-colony stimulating Factor (G-CSF) has been reported to enhance recovery from controlled cortical impact (CCI) in rodent models. G-CSF exerts actions in both the periphery (stimulation of hematopoiesis) and in the brain, where it serves as a neurotrophic factor, promoting neuronal survival and stimulating neural stem/progenitor cell proliferation in the hippocampus. In order to distinguish the direct CNS actions of G-CSF from its peripheral actions, experiments were designed to block the recruitment of peripheral monocytes to the site of the lesion produced by CCI. The selective C-C motif receptor 2 (CCR2) antagonist (RS504303) was co-administered with G-CSF for three days after CCI in a chimeric mouse previously transplanted with GFP-expressing (GFP+) blood stem-progenitor cells. Results: The drug significantly impaired infiltration of GFP+ bone marrow-derived cells to the frontal cortex and striatum without impeding recovery performance and hippocampal neurogenesis in the behavioral test, the Radial Arm Water Maze (RAWM). Administration of the CCR2 antagonist alone, without G-CSF, was effective in promoting recovery in RAWM. These results support the hypothesis that the direct action of G-CSF on neural cells, independent of its hematopoietic effects, is primarily responsible for enhanced recovery from CCI. In addition, this study confirms the importance of CCR2 and its ligand, monocyte chemotactic protein-1 (MCP-1), in mediating the inflammatory response following CCI.
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影响因子：
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作者：
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