Age-Dependent Regenerative Responses in the Striatum and Cortex after Hypoxia-Ischemia
Age-Dependent Regenerative Responses in the Striatum and Cortex after Hypoxia-Ischemia
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DOI：
10.1038/jcbfm.2008.124
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发表时间：
2009-02
影响因子：
6.3
通讯作者：
Changlian Zhu;Lin Qiu;Xiaoyang Wang;Fa-lin Xu;M. Nilsson;C. Cooper-Kuhn;H. Kuhn;K. Blomgren
中科院分区：
文献类型：
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作者：
Changlian Zhu;Lin Qiu;Xiaoyang Wang;Fa-lin Xu;M. Nilsson;C. Cooper-Kuhn;H. Kuhn;K. Blomgren
用5-溴-2-脱氧尿苷（5-bromo-2-deoxyuridine，5-bro-2-deoxyuridine）标记未成熟（P9）和幼年（P21）小鼠纹状体和皮质，观察缺氧缺血（hypoxia-ischemia，HI）后的再生反应。HI刺激未成熟的生长中的大脑中的纹状体和皮层中的新细胞的形成（P9），但是当大脑生长完成时（P21），增殖仅在纹状体中被刺激，而在皮层中不被刺激。然而，P21的相对增加（460%）高于P9纹状体（50%），尽管从P21的较低水平开始。从这个较低的水平开始，HI诱导的P21纹状体的增殖达到与P9纹状体相同的水平，但不更高。表型分析显示，低水平的神经发生仍然存在于非缺血性P9皮质和纹状体，但仅在纹状体在P21。缺血诱导的神经发生仅见于P9纹状体。缺血诱导的胶质细胞生成发生在P9和P21纹状体以及P9皮质，但不发生在P21皮质。因此，纹状体的再生反应强于皮质，P9强于P21皮质。缺血诱导的最大变化是P21纹状体小胶质细胞增加了49倍，这伴随着炎症增加，这是通过CCL 2和白细胞介素18阳性细胞的大小和数量来判断的。
Regenerative responses after hypoxia-ischemia (HI) were investigated in the immature (P9) and juvenile (P21) mouse striatum and cortex by postischemic 5-bromo-2-deoxyuridine labeling and phenotyping of labeled cells 4 weeks later. HI stimulated the formation of new cells in striatum and cortex in immature, growing brains (P9), but when brain growth was finished (P21) proliferation could be stimulated only in striatum, not in cortex. However, the relative increase was higher in P21 (460%) than P9 striatum (50%), though starting from a lower level at P21. Starting from this lower level, HI-induced proliferation in P21 striatum reached the same level as in P9 striatum, but not higher. Phenotyping revealed that low levels of neurogenesis were still present in nonischemic P9 cortex and striatum, but only in striatum at P21. Ischemia-induced neurogenesis was found only in P9 striatum. Ischemia-induced gliogenesis occurred in P9 and P21 striatum as well as P9 cortex, but not in P21 cortex. Hence, the regenerative response was stronger in striatum than cortex, and stronger in P9 than P21 cortex. The biggest ischemia-induced change was the 49-fold increase in P21 striatal microglia, and this was accompanied by increased inflammation, as judged by the size and numbers of CCL2- and interleukin-18-positive cells.