Mechanism of mild hypothermia induced cold shock protein protecting neural stem cells

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-09-18 DOI:10.1016/j.brainresbull.2025.111555

Yuanhui Sun , Jingwen Xue , Liangliang Zhang , Zhichao Zhang , Sha Sha , Qi Sun , Lan Gao , Hao Li , Qindong Shi

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引用次数: 0

Abstract

Cardiac arrest (CA) is a leading cause of death in humans. Our previous research confirmed that after CA/cardiopulmonary resuscitation, mild therapeutic hypothermia (MH) promotes neurogenesis in the brain and earlier expression of RNA-binding motif protein 3 (RBM3) in the cerebral cortex and hippocampus of rats. However, the mechanism underlying RBM3 regulating MH-induced neurogenesis remains unclear. This study simulated I/R injury after CA by oxygen-glucose deprivation/reperfusion (OGD/R) of mouse NSCs to determine whether RBM3 mediates the neuroprotective effects of MH in neural stem cells (NSCs) after ischemia-reperfusion (I/R) injury and whether this mechanism involves the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. The experimental results showed that the number of newborn NSCs increased significantly in the hypothermic group on days 3 and 5 after OGD/R injury compared with the normothermic group, and the apoptosis of NSCs decreased significantly, we also found that the proportion of NSCs differentiated into neuroglial cells decreased, while the proportion of NSCs differentiated into neurons increased. In NSCs, MH increased the expression of RBM3 after OGD/R injury and activated the PI3K/AKT signaling pathway. By inhibiting this pathway, the effects of MH on promoting NSCs’ proliferation and differentiation and inhibiting their apoptosis were eliminated.

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亚低温诱导的冷休克蛋白保护神经干细胞的机制。

心脏骤停（CA）是人类死亡的主要原因。我们之前的研究证实，在CA/心肺复苏后，轻度治疗性低体温（mild therapeutic hypothermia， MH）可促进大鼠大脑神经发生，并促进大脑皮层和海马中rna结合基序蛋白3 （RBM3）的早期表达。然而，RBM3调控mh诱导的神经发生的机制尚不清楚。本研究通过氧-葡萄糖剥夺/再灌注（OGD/R）模拟小鼠NSCs CA后I/R损伤，以确定RBM3是否介导MH对缺血-再灌注（I/R）损伤后神经干细胞（NSCs）的神经保护作用，以及该机制是否涉及磷酸肌肽3激酶(PI3K)/蛋白激酶B （AKT）信号通路。实验结果显示，与常温组相比，低温组OGD/R损伤后第3天和第5天新生NSCs数量明显增加，NSCs的凋亡明显减少，我们还发现分化为神经胶质细胞的NSCs比例减少，而分化为神经元的NSCs比例增加。在NSCs中，MH增加OGD/R损伤后RBM3的表达，激活PI3K/AKT信号通路。通过抑制该通路，可消除MH促进NSCs增殖分化和抑制其凋亡的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.