Shanghai Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Kongjiang Road 1665, Shanghai 200092, China.
Brain Res. 2013 Oct 16;1535:38-51. doi: 10.1016/j.brainres.2013.08.006. Epub 2013 Aug 29.
Mounting evidence suggests that endogenous progenitor cells may initiate cerebral WM repair. This study was designed to determine whether endogenous glial progenitor cells derived from either the subventricular zone (SVZ) or the white matter (WM) contribute to WM repair in a neonatal rat model of ischemic periventricular leukomalacia (PVL). Additionally, the role of G protein-coupled receptor 17 (GPR17), recently shown to act as a sensor for WM damage, was explored to assess its potential recruitment and activation of endogenous glial progenitor cells for such WM self-repair. Our in vivo and in vitro models consisted of five-day-old neonatal rats or cultured glial progenitor cells derived from both the SVZ and WM of these rats, randomly divided into sham/control and induced ischemic PVL/oxygen-glucose deprivation (OGD) groups. The WM of all PVL rats showed either mild or severe histopathological changes, with significantly increased in vivo apoptosis and poor myelination compared to those of the sham group. Significantly more apoptotic and necrotic cells were also detected in the OGD glial progenitor cell cultures derived from the SVZ and WM at all time intervals. The glial progenitor cells were significantly increased in both the SVZ (NG2⁺/GPR17⁻/BrdU⁺) and WM (NG2⁺/GPR17⁺/BrdU⁺) within 72 h after PVL; preOLs were also increased significantly in both the SVZ (O4⁺/GPR17⁻/BrdU⁺) and WM (O4⁺/GPR17⁺/BrdU⁺) within 7d after PVL in vivo or OGD in vitro. However, the more differentiated CNPase⁺/GPR17⁻/BrdU⁺ and MBP⁺/GPR17⁻/BrdU⁺ OLs in the SVZ and WM remained significantly less than those in the sham groups up to 14d or 21d after OGD or PVL, respectively. Hence, both the WM and SVZ were found to be potential endogenous sources of glial progenitor cells for WM repair in PVL rats. However their endogenous self-repair capacity appeared to be limited, since the more mature OLs did not completely recover from experimental ischemia, even after 14-21d.
越来越多的证据表明，内源性祖细胞可能启动脑白质修复。本研究旨在确定源自脑室下区（SVZ）或白质（WM）的内源性神经胶质祖细胞是否有助于新生大鼠缺血性脑室周围白质软化症（PVL）模型的 WM 修复。此外，还探讨了最近被证明作为 WM 损伤传感器的 G 蛋白偶联受体 17（GPR17）的作用，以评估其对 WM 自我修复的内源性神经胶质祖细胞的潜在募集和激活作用。我们的体内和体外模型包括 5 日龄新生大鼠或源自这些大鼠 SVZ 和 WM 的培养神经胶质祖细胞，随机分为假手术/对照组和诱导缺血性 PVL/氧葡萄糖剥夺（OGD）组。所有 PVL 大鼠的 WM 均显示出轻度或重度组织病理学改变，与假手术组相比，体内细胞凋亡明显增加，髓鞘形成不良。在所有时间间隔，源自 SVZ 和 WM 的 OGD 神经胶质祖细胞培养物中也检测到明显更多的凋亡和坏死细胞。在 PVL 后 72 小时内，SVZ（NG2⁺/GPR17⁻/BrdU⁺）和 WM（NG2⁺/GPR17⁺/BrdU⁺）中的神经胶质祖细胞均明显增加；在体内 PVL 后 7 天或体外 OGD 后，SVZ（O4⁺/GPR17⁻/BrdU⁺）和 WM（O4⁺/GPR17⁺/BrdU⁺）中的前 OL 也明显增加。然而，在 OGD 或 PVL 后 14 天或 21 天，SVZ 和 WM 中的更分化的 CNPase⁺/GPR17⁻/BrdU⁺和 MBP⁺/GPR17⁻/BrdU⁺OL 仍明显少于假手术组。因此，在 PVL 大鼠中，WM 和 SVZ 均被发现是 WM 修复的内源性神经胶质祖细胞潜在来源。然而，它们的内源性自我修复能力似乎有限，因为即使在 14-21 天后，实验性缺血后也未能完全恢复更成熟的 OL。
