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一种自由基清除剂可保护海马齿状回颗粒下层区的神经祖细胞免受 X 射线照射后的细胞死亡。

A free-radical scavenger protects the neural progenitor cells in the dentate subgranular zone of the hippocampus from cell death after X-irradiation.

机构信息

Department of Neurosurgery, Nagoya University School of Medicine, Japan.

出版信息

Neurosci Lett. 2010 Nov 12;485(1):65-70. doi: 10.1016/j.neulet.2010.08.065. Epub 2010 Sep 9.

Abstract

It has been elucidated that cognitive dysfunction following cranial radiotherapy might be linked to the oxidative stress-induced impairment of hippocampal neurogenesis that is mediated by proliferating neural stem or progenitor cells. The novel free-radical scavenger edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been clinically used to reduce neuronal damage following ischemic stroke. Previously, we reported that the free-radical scavenger, edaravone, which is currently used to treat patients with brain ischemia, protected cultured human neural stem cells (NSCs) from radiation-induced cell death; the protective effect was observed more significantly in NSCs than in brain tumor cells. Here, in animal models, we demonstrate that edaravone protects neurons in the subgranular zone (SGZ) of the dentate gyrus of the hippocampus from cell death after irradiation. Moreover, edaravone protected spatial memory retention deficits as determined by Morris water maze tests. Our study may shed some light on the beneficial effects of free-radical scavengers in impaired neurogenesis following cranial radiation therapy.

摘要

已经阐明,颅放射治疗后认知功能障碍可能与氧化应激诱导的海马神经发生损伤有关,这种损伤是由增殖的神经干细胞或祖细胞介导的。新型自由基清除剂依达拉奉(3-甲基-1-苯基-2-吡唑啉-5-酮)已临床用于减少缺血性中风后神经元损伤。先前,我们报道自由基清除剂依达拉奉可保护体外培养的人神经干细胞(NSCs)免受辐射诱导的细胞死亡;在 NSCs 中的保护作用比在脑肿瘤细胞中更显著。在这里,在动物模型中,我们证明依达拉奉可保护海马齿状回颗粒下区(SGZ)的神经元免受照射后的细胞死亡。此外,依达拉奉可保护空间记忆保留缺陷,这通过 Morris 水迷宫测试来确定。我们的研究可能为自由基清除剂在颅放射治疗后神经发生受损中的有益作用提供一些启示。

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