Koketsu Daisuke, Furuichi Yasuhisa, Maeda Masashi, Matsuoka Nobuya, Miyamoto Yusei, Hisatsune Tatsuhiro
Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba 277-8562, Japan.
Exp Neurol. 2006 May;199(1):92-102. doi: 10.1016/j.expneurol.2006.03.012. Epub 2006 May 18.
Adult neurogenesis is modulated by growth factors, physical conditions, and other alterations in the physical microenvironment. We studied the effects of focal ischemia on neurogenesis in the subventricular zone (SVZ), olfactory bulb (OB), and hippocampal dentate gyrus (DG) (known to be persistent neurogenic regions) in the adult non-human primate, the cynomolgus monkey. Three monkeys underwent middle cerebral artery occlusion-induced focal ischemia and were given multiple BrdU injections during the first 2 weeks after ischemia. Twenty-eight days later, the animals were perfused. The number of new neurons (3182 +/- 408/mm3) in the ipsilateral DG of ischemic monkeys was 4.7-fold that in the DG of non-operated monkeys. The number of new neurons (9176 +/- 2295/mm3) in the ipsilateral olfactory bulb of ischemic monkeys was 18.0-fold that in normal olfactory bulb. These observations suggest an increase in the number of new OB neurons, as well as new DG neurons, after focal ischemia in a primate. This substantial increase in new neurons after focal ischemia could result from the enhancement of cell proliferation rather than a change in the rate of cell commitment. Of the three monkeys subjected to ischemia, only one animal possessed a unique progenitor cell type at the most anterior aspect of the ipsilateral SVZ. Within this region, a short migration (approximately 500 microm) of doublecortin-expressing immature neuronal progenitor cells was observed.
成体神经发生受生长因子、身体状况以及物理微环境中的其他变化调节。我们研究了局灶性缺血对成年食蟹猴(非人灵长类动物)脑室下区(SVZ)、嗅球(OB)和海马齿状回(DG)(已知为持续神经发生区域)神经发生的影响。三只猴子接受大脑中动脉闭塞诱导的局灶性缺血,并在缺血后的前两周内多次注射溴脱氧尿苷(BrdU)。28天后,对动物进行灌注。缺血猴子同侧DG中新神经元的数量(3182±408/mm³)是未手术猴子DG中数量的4.7倍。缺血猴子同侧嗅球中新神经元的数量(9176±2295/mm³)是正常嗅球中数量的18.0倍。这些观察结果表明,在灵长类动物局灶性缺血后,嗅球和齿状回中新神经元的数量增加。局灶性缺血后新神经元数量的大幅增加可能是由于细胞增殖增强,而非细胞分化速率改变所致。在三只接受缺血的猴子中,只有一只动物在同侧SVZ的最前端拥有一种独特的祖细胞类型。在该区域内,观察到表达双皮质素的未成熟神经祖细胞有短距离迁移(约500微米)。