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

1.采用大鼠大脑中动脉闭塞（MCAO）模型，观察大鼠局灶性脑缺血后梗死周围区神经发生及室下区（SVZ）和齿状回（DG）神经祖细胞增殖的变化。于缺血后1、2、3、4、6、8周处死动物前，用5-溴-2 ′-脱氧尿苷-5 ′-单磷酸（5-BrdU）标记心肌细胞。为了评价细胞特异性，进行NeuN、GFAP和IB 4免疫标记。在脑缺血后3周至8周，脑梗死周围区的大脑皮质中，我们发现BrdU阳性细胞共表达成熟的神经元标记物NeuN。另一方面，我们观察到缺血后双侧半球DG和SVZ的BrdU阳性细胞增加。我们报道了大鼠局灶性脑缺血后SVZ和DG区皮质神经发生和神经祖细胞增殖的情况。由于皮层神经发生仍存在争议，我们需要做进一步的研究来揭示神经发生的实际情况. SOD 1过表达小鼠表现出神经干细胞在衰老过程中的保存和局灶性脑缺血后神经干细胞的增加，我们研究了SOD 1与衰老过程中神经干细胞增殖的相关性，作为慢性氧化应激（研究1）和短暂局灶性脑缺血诱导的急性氧化应激（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中的神经干细胞显着增加（p=0.0001）。在研究2中，使小鼠经受30分钟MCAO。转基因小鼠DG区神经干细胞的数量明显多于野生型小鼠（p<0.05）。我们的研究结果表明，慢性和急性氧化应激可能会抑制神经干细胞的增殖，SOD 1可能在其增殖中发挥关键作用。

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.