Jin-qiao Sun, Bin Sha, Wen-hao Zhou, Yi Yang
Institute of Pediatrics, Children's Hospital, Fudan University, Shanghai, China.
Brain Dev. 2009 May;31(5):331-40. doi: 10.1016/j.braindev.2008.06.005. Epub 2008 Jul 26.
A little is known about the proliferation and fate of neural stem cells in the subventricular zone (SVZ) after cerebral ischemia. However, how endogenous neural stem cells are activated in the premature brain is not clear, although basic fibroblast growth factor (bFGF) is important in neurogenesis. To investigate the effect of bFGF on the proliferation and differentiation of neural stem cells after brain ischemia, we observed cellular changes in the subventricular zone (SVZ) of 3-day-old rats (approximately equivalent to premature infants) using immunofluorescence assays, Western blot analysis, and real-time quantitative PCR methods. The bilateral common carotid artery (BCCA) was occluded in 108 animals, then half received bFGF 10ng/g. Besides, 54 rats without ischemia as normal control. Proliferating cells were labeled by bromodeoxyuridine (BrdU) through intraperitoneal injection in a pulsed or a cumulative protocol. Rats were killed at 4, 7, and 14 days after ischemic injury. The number of proliferating cells in the SVZ in bFGF-treated rats was higher than that in untreated rats; bFGF also promoted neural stem cell differentiation into neurons, astrocytes, and oligodendrocytes. Western blot analysis and real-time quantitative PCR assays confirmed these results. We suggest that bFGF promotes the repair of ischemia brain injury through increasing the proliferation of neural stem cells and their differentiation into neurons, astrocytes, and oligodendrocytes.
关于脑缺血后室管膜下区（SVZ）神经干细胞的增殖和命运，人们了解甚少。然而，尽管碱性成纤维细胞生长因子（bFGF）在神经发生中很重要，但内源性神经干细胞在未成熟大脑中是如何被激活的尚不清楚。为了研究bFGF对脑缺血后神经干细胞增殖和分化的影响，我们使用免疫荧光分析、蛋白质免疫印迹分析和实时定量PCR方法，观察了3日龄大鼠（大约相当于早产儿）室管膜下区（SVZ）的细胞变化。对108只动物进行双侧颈总动脉（BCCA）闭塞，然后其中一半接受10ng/g的bFGF。此外，54只无缺血的大鼠作为正常对照。通过腹腔注射以脉冲或累积方案用溴脱氧尿苷（BrdU）标记增殖细胞。在缺血损伤后4、7和14天处死大鼠。bFGF处理的大鼠SVZ中增殖细胞的数量高于未处理的大鼠；bFGF还促进神经干细胞分化为神经元、星形胶质细胞和少突胶质细胞。蛋白质免疫印迹分析和实时定量PCR分析证实了这些结果。我们认为，bFGF通过增加神经干细胞的增殖及其向神经元、星形胶质细胞和少突胶质细胞的分化来促进缺血性脑损伤的修复。
