The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia
The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia-ischemia
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DOI：
10.1038/sj.cdd.4401545
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发表时间：
2005-02-01
影响因子：
12.4
通讯作者：
Blomgren, K
中科院分区：
文献类型：
--
作者：
Zhu, C;Wang, X;Blomgren, K
在出生后第 5 天、第 9 天、第 21 天和第 60 天，C57/BL6 雄性小鼠诱导单侧缺氧缺血 (HI)，分别对应于早产儿、足月儿、青少年和成人大脑的发育。调整 HI 持续时间以获得所有年龄段的相似程度的脑损伤。未成熟大脑中的细胞凋亡机制（细胞凋亡诱导因子的核易位、细胞色素 c 释放和 caspase-3 激活）比青少年和成人大脑中明显数倍。坏死相关的钙蛋白酶激活在所有年龄段都是相似的。 CA1 亚区从 P5 和 P9 的凋亡相关神经元死亡转变为 P21 和 P60 的坏死相关钙蛋白酶激活。所有年龄段的氧化应激（硝基酪氨酸形成）也相似。根据自噬体相关标记物 LC-3 II 判断，自噬在成人大脑中更为明显。据我们所知，这是第一份证明 AIF 介导的细胞死亡的发育调节以及脑损伤模型中自噬参与的报告。
Unilateral hypoxia-ischemia (HI) was induced in C57/BL6 male mice on postnatal day (P) 5, 9, 21 and 60, corresponding developmentally to premature, term, juvenile and adult human brains, respectively. HI duration was adjusted to obtain a similar extent of brain injury at all ages. Apoptotic mechanisms (nuclear translocation of apoptosis-inducing factor, cytochrome c release and caspase-3 activation) were several-fold more pronounced in immature than in juvenile and adult brains. Necrosis-related calpain activation was similar at all ages. The CA1 subfield shifted from apoptosis-related neuronal death at P5 and P9 to necrosis-related calpain activation at P21 and P60. Oxidative stress (nitrotyrosine formation) was also similar at all ages. Autophagy, as judged by the autophagosome-related marker LC-3 II, was more pronounced in adult brains. To our knowledge, this is the first report demonstrating developmental regulation of AIF-mediated cell death as well as involvement of autophagy in a model of brain injury.