Accumulation of macrophage-like cells expressing NG2 proteoglycan and Iba1 in ischemic core of rat brain after transient middle cerebral artery occlusion

Accumulation of macrophage-like cells expressing NG2 proteoglycan and Iba1 in ischemic core of rat brain after transient middle cerebral artery occlusion
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DOI:
10.1038/sj.jcbfm.9600519
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发表时间:
2008-01-01
影响因子:
6.3
通讯作者:
Tanaka, Junya
Tanaka, Junya
中科院分区:
医学1区
文献类型:
--
作者:
Matsumoto, Hiroaki;Kumon, Yoshiaki;Tanaka, Junya

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虽然缺血性脑损伤核心区的神经元和胶质细胞不可避免地发生变性,但仍有许多细胞,特别是免疫细胞浸润并在其中存活,这些浸润细胞在受损脑组织的再生和修复中可能发挥一定的作用。在这项研究中,我们的特点是巨噬细胞样细胞,积累在大鼠大脑缺血的核心,其右侧大脑中动脉短暂闭塞90分钟。许多积累的巨噬细胞样细胞表达Iba 1,巨噬细胞/小胶质细胞的标志物,以及NG 2硫酸软骨素蛋白聚糖(NG 2),它已被认为是少突胶质细胞祖细胞的标志物。这种巨噬细胞样细胞被称为BINC(脑Iba 1(+)/NG 2(+)细胞),以区别于NG 2(-)/Iba 1(+)或NG 2(+)/Iba 1(-)细胞,后者也存在于病灶周围和对侧半球。电子显微镜显示NG 2沿着细胞质膜定位,这些细胞具有许多吞噬体和不规则形状或肾形的富含异染色质的核,这是单核细胞/巨噬细胞的特征。脑内Iba 1(+)/NG 2(+)细胞高度增殖,在再灌注后7 d达到高峰。NG 2的免疫印迹分析揭示了两个NG 2的存在:一个由BINCs表达,分子量为300 kDa,另一个在对侧半球中发现,分子量为290 kDa。结合NG 2的多种功能,BINCs可能不仅参与变性细胞的吞噬,而且参与损伤核心的愈合和再生。
Although neurons and glia inevitably undergo degeneration in the core of ischemic lesions, many cells, particularly immune cells, infiltrate the core and survive in it. Such infiltrating cells may play certain roles in the regeneration and repair of damaged brain tissues. In this study, we characterized macrophage-like cells that accumulated in the ischemic core of a rat brain whose right middle cerebral artery was transiently occluded for 90 mins. Many of the accumulated macrophage-like cells expressed Iba1, a marker of macrophages/microglia, as well as NG2 chondroitin sulfate proteoglycan (NG2), which has been recognized as a marker of oligodendrocyte progenitor cells. Such macrophage-like cells were termed BINCs (brain Iba1(+)/NG2(+) cells) to distinguish them from NG2(-)/Iba1(+) or NG2(+)/Iba1(-) cells that were also present in the perilesion and the contralateral hemisphere. Electron microscopy showed the localization of NG2 along the plasma membrane of cells that had many phagosomes and irregular-shaped or reniform heterochromatin-rich nuclei, which are characteristics of monocytes/macrophages. Brain Iba1(+)/NG2(+) cells were highly proliferative and their number peaked at 7 days post-reperfusion. An immunoblot analysis of NG2 revealed the presence of two NG2s: one expressed by BINCs with a molecular weight of 300 kDa, and the other found in the contralateral hemisphere with a molecular weight of 290 kDa. Taken the various functions of NG2, BINCs may be involved in not only phagocytosis of degenerated cells but also the healing and regeneration of lesion cores.