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STEM CELLS:阻碍脑卒中后神经干细胞再生的“元凶”找到了

2013-09-13 驻地记者 孙国根 中国医学论坛报

复旦大学医学神经生物学国家重点实验室、脑科学研究院赵冰樵教授带领其研究团队,经3年多艰苦攻关首次发现,脑内一种名叫“caspase-3”的分子,一旦被激活,不仅在人的脑卒中发生初期起“细胞杀手”的作用,而且在脑卒中的恢复期继续起“破坏作用” ;但更重要的是,该研究团队发现药物可以抑制caspase-3的破坏作用,从而促进脑卒中后神经干细胞的再生。目前该成果已刊登在最新一期的著名学

复旦大学医学神经生物学国家重点实验室、脑科学研究院赵冰樵教授带领其研究团队,经3年多艰苦攻关首次发现,脑内一种名叫“caspase-3”的分子,一旦被激活,不仅在人的脑卒中发生初期起“细胞杀手”的作用,而且在脑卒中的恢复期继续起“破坏作用” ;但更重要的是,该研究团队发现药物可以抑制caspase-3的破坏作用,从而促进脑卒中后神经干细胞的再生。目前该成果已刊登在最新一期的著名学术期刊《干细胞》(Stem Cells)杂志上,引起世界医学界关注。【原文下载】

脑卒中所造成的神经功能障碍,临床上至今尚无有效的治疗手段。近年来的研究发现,成年大脑中风后有神经再生的能力,人一旦中风,这些新生的神经干细胞会 “主动”迁移到脑损伤区的周边, 并“分化”为成熟的神经细胞后参与脑功能的修复工作。但是,脑损伤后,这些新生的神经干细胞的存活能力和形成成熟神经细胞的能力都非常有限, 而且把神经干细胞移植到脑内,其迁移、分化和整合到正常的神经元网络中也十分困难。因此,脑卒中后神经干细胞再生和分化机制研究,以及如何促进神经元的有效新生, 如何重塑脑中风后受损的神经功能一直是困扰脑中风研究领域的重大瓶颈问题。

赵冰樵研究团队从“Caspase-3在脑卒中后为何被激活?”这一命题入手,经3年多研究首次发现,原来被称为“细胞杀手”的caspase-3是脑内神经干细胞再生的重要抑制分子,也是一种关键的导致正常细胞死亡的执行因子。但是,赵冰樵研究团队在研究中意外发现,脑卒中虽然引起“caspase-3”在小鼠脑内神经干细胞中大量聚集,即便采用多种实验手段,这些caspase-3也并不执行让细胞凋亡的功能。那么caspase-3到底起什么作用呢? 后来他们的进一步研究证实,使用药物可以抑制caspase-3的活性,从而促进脑卒中后神经干细胞的再生 , 并可加快新生神经干细胞向成熟神经细胞即神经元的转化, 从而协助脑损伤后的功能修复,而神经元在修复过程中是起主导作用的一类神经细胞。

以往的研究仅证明抑制caspase-3的活性后,对急性脑卒中具有保护作用, 但赵冰樵研究团队的研究结果进一步证明caspase-3在脑卒中后继续有“破坏作用”。该成果不但对临床上如何促进脑卒中后的神经再生, 而且对开发既保护脑损伤,又促进脑损伤后功能重塑、找到新型治疗药物新靶点具有重要意义。

原文下载
Wenying Fan,Yiqin Dai, Haochen Xu,Ximin Zhu,Ping Cai,Lixiang Wang, Chungang Sun,Changlong Hu,Ping Zheng,Bing-Qiao Zhao.Caspase-3 Modulates Regenerative Response after Stroke.STEM CELLS 13 AUG 2013

    

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    2014-03-09 维他命
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