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脑中风后的大脑可以通过调节lncRNA FosDT进行保护

Suresh L Mehta¹, Bharath Chelluboina¹, Kahlilia C Morris-Blanco^1,2

¹Department of Neurological Surgery University of Wisconsin, Madison, WI, USA.

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

|November 7, 2023

概括

用siRNA针对Fos下游转录 (FosDT) 提供了中风后的神经保护. 这种中风治疗改善了运动功能,并减少了各种动物模型的脑损伤,无论年龄或性别.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
遗传学遗传学是一种遗传学.

背景情况:

脑卒中诱导显著的二次大脑损伤.
长非编码RNA的Fos下游转录 (FosDT) 与中风后的神经元损伤有关.
之前的研究表明,FosDT的淘汰或删除具有神经保护作用.

研究的目的:

评估FosDTsiRNA在中风治疗中的治疗潜力.
评估FosDTsiRNA在各种动物模型和条件中的有效性.
阐明FosDT在中风中的作用背后的分子机制.

主要方法:

动物中暂时中脑动脉封闭 (MCAO) 模型.
在重输后的不同时间点给予FosDT siRNA.
通过旋杆,光束行走和粘合剂去除测试来评估运动功能的恢复.
测量心脏病发作的大小.
研究涉及REST和NF-κB的分子途径.

主要成果:

给予FosDT siRNA显著改善了运动功能的恢复,并减少了成年和老年老鼠的两性心脏病大小.
延迟使用FosDT siRNA也显示出显著的治疗效益.
在正常和糖尿病小鼠中,FosDT siRNA增强了功能恢复.
转录因子REST调解FosDT诱导的神经元损伤,而NF-κB调节FosDT的表达.

结论:

FosDT是一种可行的治疗点,可以缓解中风后的二次大脑损伤.
FosDT siRNA 具有有利的治疗窗口和广泛的适用性,跨性别,年龄,物种和并发症.
准FosDT有望提高中风后的功能恢复.

关键词:

大脑缺血症的大脑缺血症伴随性疾病发生率.神经保护神经保护没有编码的RNA.治疗疗法治疗疗法治疗疗法转录规则转录规则转录规则

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