Spatictemporal profile of neural stern cell in SOD1 overexpressin mice following cerebral ischemia

1. 大鼠局灶性脑缺血后梗死周围区皮质神经发生及脑室下区和齿状回神经祖细胞增殖。雄性Sprague-Dawley大鼠大脑中动脉闭塞60分钟。在缺血后1、2、3、4、6和8周牺牲动物之前，通过累积给药对增殖细胞进行5-溴-2′-脱氧尿苷-5′-单磷酸（BrdU）标记。采用NeuN、GFAP和IB4免疫标记法评价细胞特异性。在缺血后3周至8周，我们发现BrdU阳性细胞在梗死周围区大脑皮层共表达成熟神经元标志物NeuN。另一方面，我们观察到缺血后双侧半球DG和SVZ BrdU阳性细胞增多。我们报道了大鼠短暂局灶性脑缺血后SVZ和DG皮层神经发生和神经祖细胞增殖。由于皮质神经发生仍有争议，我们需要做进一步的研究来揭示神经发生的实际情况。SOD1过表达小鼠在衰老过程中表现出神经干细胞的保存和局灶性脑缺血后神经干细胞的增加。我们研究了SOD1与衰老过程中神经干细胞增殖的关系，如慢性氧化应激（研究1）和短暂局灶性脑缺血引起的急性氧化应激（研究2）。在研究1中，16个月大的转基因小鼠与野生型相比，SVZ中的神经干细胞显著增加（p=0.0001）。在研究2中，小鼠接受30分钟的MCAO。转基因小鼠DG中神经干细胞数量的增加显著高于野生型（p<0.05）。我们的研究结果表明，慢性和急性氧化应激可能抑制神经干细胞的增殖，SOD1可能在其增殖中起关键作用。

1. Cortical neurogenesis in periinfarcted zone and proliferation of neural progenitors in subventricular zone (SVZ) and dentate gyrus (DG) following transient focal cerebral ischemia in rats.Male Sprague-Dawley rats were subjected to 60 minutes middle cerebral artery occlusion (MCAO). Proliferating cells were labeled 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU) by cumulative administration before sacrificing animals at 1,2,3,4,6, and 8weeks after ischemia. For the evaluation of cell specificity, NeuN, GFAP and IB4 immunolabeling were performed. In cerebral cortex of periinfarcted zone, we demonstrated BrdU positive cells co-express mature neuronal marker NeuN from 3weeks to 8weeks after ischemia. On the other hand, we observed increasing BrdU positive cells in DG and SVZ of bilateral hemisphere after ischemia. We reported cortical neurogenesis and proliferation of neural progenitors in SVZ and DG following transient focal cerebral ischemia in rats. Since cortical neurogenesis is still controversial, we need to do further investigation to disclose the actual condition of neurogenesis.2. SOD1 overexpressing mice exhibit preservation of neural stem cells in aging and increase of neural stem cells following focal cerebral ischemia.We investigated the correlation between SOD1 and the proliferation of neural stem cells in aging as chronic oxidative stress (study 1) and acute oxidative stress induced by transient focal cerebral ischemia (study 2) in these mice. In study 1, 16-month-old transgenic mice showed a significant increase of neural stem cells in the SVZ compared with wild-type (p=0.0001). In study 2, mice were subjected to 30 min MCAO. The increase of neural stem cells in the DG in transgenic mice was significantly greater than that in wild-type (p<0.05). Our results suggest that chronic and acute oxidative stress may inhibit the proliferation of neural stem cells and that SOD1 may play a key role in their proliferation.