Matsumoto Hiroaki, Kumon Yoshiaki, Watanabe Hideaki, Ohnishi Takanori, Shudou Masachika, Chuai Miao, Imai Yoshinori, Takahashi Hisaaki, Tanaka Junya
Department of Neurosurgery, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
J Cereb Blood Flow Metab. 2008 Jan;28(1):149-63. doi: 10.1038/sj.jcbfm.9600519. Epub 2007 Jun 13.
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.
尽管神经元和神经胶质细胞在缺血性损伤核心区域不可避免地会发生变性,但许多细胞,尤其是免疫细胞,会浸润到核心区域并在其中存活。这些浸润细胞可能在受损脑组织的再生和修复中发挥一定作用。在本研究中,我们对在大鼠脑缺血核心区域积聚的巨噬细胞样细胞进行了表征,该大鼠的右侧大脑中动脉被短暂闭塞90分钟。许多积聚的巨噬细胞样细胞表达Iba1(巨噬细胞/小胶质细胞的标志物)以及NG2硫酸软骨素蛋白聚糖(NG2),NG2已被公认为少突胶质细胞前体细胞的标志物。这种巨噬细胞样细胞被称为BINCs(脑Iba1(+)/NG2(+)细胞),以区别于也存在于损伤周边和对侧半球的NG2(-)/Iba1(+)或NG2(+)/Iba1(-)细胞。电子显微镜显示NG2定位于具有许多吞噬体和不规则形状或肾形富含异染色质核的细胞的质膜上,这些是单核细胞/巨噬细胞的特征。脑Iba1(+)/NG2(+)细胞具有高度增殖性,其数量在再灌注后7天达到峰值。对NG2的免疫印迹分析显示存在两种NG2:一种由BINCs表达,分子量为300 kDa,另一种在对侧半球发现,分子量为290 kDa。鉴于NG2的各种功能,BINCs可能不仅参与变性细胞的吞噬作用,还参与损伤核心的愈合和再生。