Iba1+/NG2+ macrophage-like cells expressing a variety of neuroprotective factors ameliorate ischemic damage of the brain
Iba1+/NG2+ macrophage-like cells expressing a variety of neuroprotective factors ameliorate ischemic damage of the brain
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DOI：
10.1038/jcbfm.2009.233
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发表时间：
2010-03-01
影响因子：
6.3
通讯作者：
Tanaka, Junya
中科院分区：
文献类型：
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作者：
Smirkin, Anna;Matsumoto, Hiroaki;Tanaka, Junya
在大鼠短暂性90分钟大脑中动脉闭塞（MCAO）模型中，形成大的缺血性病变，其中巨噬细胞样细胞大量积聚，其中许多细胞表达巨噬细胞标志物Iba 1和少突胶质细胞祖细胞标志物NG 2硫酸软骨素蛋白聚糖（NG 2）;因此，这些细胞被称为BINC（脑Iba 1（+）/NG 2（+）细胞）。使用绿色荧光蛋白转基因大鼠的骨髓移植实验表明，BINCs来源于骨髓。5-再灌注后2天注射5-氟尿嘧啶（5-FU）可明显减少再灌注后7天的BINCs数量，导致大鼠坏死体积扩大，死亡率增高。当将分离的BINCs移植到5 FU加重的缺血损伤中时，损伤体积明显减小。实时定量RT-PCR显示BINCs表达编码bFGF、BMP 2、BMP 4、BMP 7、GDNF、HGF、IGF-1、PDGF-A和VEGF的mRNA。特别地，BINCs以非常高的水平表达IGF-1 mRNA。免疫组织化学染色显示，IGF-1表达的BINCs不仅在大鼠，而且在人类缺血性脑损伤中被发现。这些结果表明，骨髓来源的BINCs在缺血性脑损伤中发挥有益作用，至少部分是通过分泌神经保护因子。Journal of Cerebral Blood Flow & Metabolism（2010）30，603-615; doi：10.1038/jcbfm.2009.233; 2009年10月28日在线发表
In a transient 90-min middle cerebral artery occlusion (MCAO) model of rats, a large ischemic lesion is formed where macrophage-like cells massively accumulate, many of which express a macrophage marker, Iba1, and an oligodendrocyte progenitor cell marker, NG2 chondroitin sulfate proteoglycan (NG2); therefore, the cells were termed BINCs (Brain Iba1(+)/NG2(+) Cells). A bone marrow transplantation experiment using green-fluorescent protein-transgenic rats showed that BINCs were derived from bone marrow. 5-Fluorouracil (5FU) injection at 2 days post reperfusion (2 dpr) markedly reduced the number of BINCs at 7 dpr, causing enlargement of necrotic volumes and frequent death of the rats. When isolated BINCs were transplanted into 5FU-aggravated ischemic lesion, the volume of the lesion was much reduced. Quantitative real-time RT-PCR showed that BINCs expressed mRNAs encoding bFGF, BMP2, BMP4, BMP7, GDNF, HGF, IGF-1, PDGF-A, and VEGF. In particular, BINCs expressed IGF-1 mRNA at a very high level. Immunohistochemical staining showed that IGF-1-expressing BINCs were found not only in rat but also human ischemic brain lesions. These results suggest that bone marrow-derived BINCs play a beneficial role in ischemic brain lesions, at least in part, through secretion of neuroprotective factors. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 603-615; doi: 10.1038/jcbfm.2009.233; published online 28 October 2009