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首页> 外文期刊>The European Journal of Neuroscience >Insulin-like growth factor-1 is an endogenous mediator of focal ischemia-induced neural progenitor proliferation.
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Insulin-like growth factor-1 is an endogenous mediator of focal ischemia-induced neural progenitor proliferation.

机译：胰岛素样生长因子-1是局灶性缺血诱导的神经祖细胞增殖的内源性介质。

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摘要

The adult mammalian brain contains resident neural progenitors in the subgranular zone of the dentate gyrus (DG) and the subventricular zone (SVZ) of the lateral ventricles. The proliferation of neural progenitors increases after focal cerebral ischemia in both of these regions, but the mechanisms that promote ischemia-induced neural progenitor proliferation are not yet understood. We hypothesize that diffusible factors from the ischemic area play a role in this process as the DG is remote from the area of infarction. In this study, we observed that the peak of neural progenitor proliferation in the ipsilateral DG was between day 2 and day 4 of reperfusion after transient middle cerebral artery occlusion in adult spontaneously hypertensive rats. GeneChip and real-time PCR analysis showed a three- to 102-fold increase in the expression of 15 diffusible, mitogenic factors in the ischemic cortex at 3 days of reperfusion. Of these, insulin-like growth factor-1 (IGF-1) showed increased protein expression inthe activated astrocytes in the ischemic penumbra. In addition, the progenitors in both the SVZ and DG showed IGF-1 receptor expression. Inhibiting IGF-1 activity by introcerebroventricular infusion of IGF-1 antibody significantly prevented the ischemia-induced neural progenitor proliferation. These results indicate that IGF-1 formed in the ischemic penumbra might be one of the diffusible factors that mediate post-ischemic neural progenitor proliferation.
机译：成年哺乳动物的大脑在齿状回的亚颗粒区（DG）和侧脑室的脑室下区（SVZ）中含有常驻神经祖细胞。在这两个区域发生局灶性脑缺血后，神经祖细胞的增殖都增加了，但是促进缺血诱导的神经祖细胞增殖的机制尚不清楚。我们假设由于DG远离梗死区域，因此来自缺血区域的扩散因子在此过程中起作用。在这项研究中，我们观察到成年自发性高血压大鼠脑中动脉短暂阻塞后，同侧DG中神经祖细胞增殖的峰值在再灌注的第2天至第4天之间。 GeneChip和实时PCR分析显示，再灌注3天后，缺血皮层中15种弥散性有丝分裂因子的表达增加了3到102倍。其中，胰岛素样生长因子-1（IGF-1）在缺血性半影​​的活化星形胶质细胞中显示出增加的蛋白质表达。此外，SVZ和DG中的祖细胞均显示IGF-1受体表达。通过脑室内注入IGF-1抗体抑制IGF-1活性可显着阻止缺血诱导的神经祖细胞增殖。这些结果表明在缺血半影中形成的IGF-1可能是介导缺血后神经祖细胞增殖的扩散因子之一。

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