Kir4.1 channel activation in NG2 glia contributes to remyelination in ischemic stroke.
Kir4.1 channel activation in NG2 glia contributes to remyelination in ischemic stroke.
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NG2 神经胶质细胞中的 Kir4.1 通道激活有助于缺血性中风的髓鞘再生。
DOI：
10.1016/j.ebiom.2022.104406
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发表时间：
2023-01
期刊：
影响因子：
11.1
通讯作者：
Tong, Xiaoping
中科院分区：
文献类型：
--
作者：
Hong, Xiaoqi;Jian, Yujin;Ding, Shenghao;Zhou, Jianpo;Zheng, Xiaoli;Zhang, Huimin;Zhou, Butian;Zhuang, Canbin;Wan, Jieqing;Tong, Xiaoping
脑卒中是世界上最常见的神经系统疾病之一，临床表现为短暂或永久性脑功能障碍。它的死亡率和残疾率很高，严重影响人们的健康，降低生活质量。然而，没有有效的治疗方法可以被认为是治愈性的，还有其他不太知名的发病机制理论。因此，有必要充分了解缺血的病理生理学，并寻求新的治疗策略。我们首先检测Kir4.1通道和髓鞘蛋白（MBP）的表达在急性缺血患者的脑组织中的蛋白质免疫印迹。然后，我们建立了短暂性缺血小鼠模型（tMCAO）进行分子，细胞生物学，透射电子显微镜和药代动力学研究，以及在Kir4.1 cKO小鼠。最后，神经影像学和行为学分析被用来检查是否激活Kir4.1通道毛地黄黄酮可以有助于缺血性中风神经功能恢复。在急性缺血性脑卒中患者中，我们首次证明了Kir4.1离子通道的严重受损，这些患者的大脑皮层缺血梗死区发生了严重的轴突脱髓鞘。进一步的证据表明，在短暂性缺血小鼠模型（tMCAO）中，NG2胶质细胞中Kir4.1通道的缺陷导致轴突髓鞘丢失。用天然植物提取物治疗缺血小鼠，毛地黄黄酮增强NG2胶质细胞中的Kir4.1通道电流，从而促进轴突的髓鞘再生，减轻梗塞面积，并最终在一系列行为测试中改善运动功能。通过木樨草素治疗靶向NG2胶质细胞中表达的Kir4.1离子通道突出了缺血性卒中中迅速脑功能恢复的有效治疗策略。这项工作得到了科技部中国脑计划（2022ZD0204702，给X.T.）的赠款，（82271466、82171279、31970904、31571063）、（1510000084）、（15PJ1404600）、重大项目（2018SHZDZX05）、项目（17411954000）。
Stroke is one of the most common neurological diseases in the world and is clinically manifested by transient or permanent brain dysfunction. It has a high mortality and disability rate, which severely affects people's health and diminishes the quality of life. However, there is no efficient treatment that can be considered curative and there are other less well-known theories of pathogenesis. Therefore, it is imperative to gain a full understanding of the pathophysiology of ischemia and to seek new therapeutic strategies. We first examined Kir4.1 channel and myelin based protein (MBP) expression in brain tissues from acute ischemic patients by Western blotting. We then established a transient ischemic mouse model (tMCAO) to conduct molecular, cell biological, transmission electron microscopy and pharmacokinetic studies, as well as in Kir4.1 cKO mice. Finally, neuroimaging and behavioral analyses were used to examine whether activation of Kir4.1 channel by luteolin could contribute to neuronal functional recovery in ischemic stroke. In acute ischemic stroke patients, we first demonstrated that Kir4.1 ion channels were greatly impaired and a severe demyelination of axons occurred in ischemic infarction area of cerebral cortex in these patients. Further evidence showed that the deficits of Kir4.1 channels in NG2 glia led to the myelin loss of axons in a transient ischemic mouse model (tMCAO). Treating ischemic mice with a natural botanical extract, luteolin augmented Kir4.1 channel currents in NG2 glia and consequently promoted remyelination of axons, alleviated the infarction area and ultimately improved motor function in a series of behavioral tests. Targeting Kir4.1 ion channels expressed in NG2 glial cells by luteolin treatment highlights an effective therapeutic strategy for a prompt brain functional recovery in ischemic stroke. This work was supported by grants from the Ministry of Science and Technology China Brain Initiative (2022ZD0204702, to X.T.), the (82271466, 82171279, 31970904 and 31571063), the (1510000084), (15PJ1404600), Major Project (2018SHZDZX05) and Project (17411954000).
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影响因子：
5.3
作者：
Djukic, Biljana;Casper, Kristen B.;McCarthy, Ken D.
通讯作者：
McCarthy, Ken D.
影响因子：
3.9
作者：
Li, Lu;Pan, Guanghua;Fan, Rong;Li, Dalei;Guo, Lei;Ma, Lili;Liang, Hui;Qiu, Jiaoxue
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影响因子：
12.7
作者：
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通讯作者：
Olsen ML
DOI：
10.2147/bctt.s124860
发表时间：
2017
期刊：
Breast cancer (Dove Medical Press)
影响因子：
--
作者：
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通讯作者：
Hyder SM
影响因子：
4.4
作者：
Qiao, Huimin;Dong, Lipeng;Li, Yanhua
通讯作者：
Li, Yanhua