High-concentration hydrogen inhalation mitigates sepsis-associated encephalopathy in mice by improving mitochondrial dynamics

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2024-09-11 DOI:10.1111/cns.70021

Yan Cui, Shuqi Meng, Nannan Zhang, Jingya Liu, Lina Zheng, Wanjie Ma, Yu Song, Zhiwei Wang, Yuehao Shen, Jianfeng Liu, Keliang Xie

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Abstract

Background

Sepsis-associated encephalopathy (SAE) is a neuronal injury with poor prognosis. Mitochondrial dysfunction is critical in SAE development, and hydrogen gas (H₂) has a protective effect on septic mice. This study aimed to investigate the effect of high concentration (67%) of H₂ on SAE and whether it is related to mitochondrial biogenesis and mitochondrial dynamics.

Methods

A mouse sepsis model was induced by cecal ligation and puncture. The mice inhalated 67% H₂ for 1 h at 1 and 6 h post-surgery, respectively. The 7-day survival rate was recorded. Cognitive function was assessed using the Y-maze test and Morris water maze test. Serum inflammatory factors, antioxidant enzymes, as well as mitochondrial function indexes including mitochondrial membrane potential (MMP) and ATP in the hippocampal tissue were evaluated 24 h after surgery. Mitochondrial dynamic proteins (DRP1 and MFN2) and biosynthetic proteins (PGC-1α, NRF2, and TFAM) in the hippocampal tissue were detected. Moreover, the morphology of mitochondria was observed by transmission electron microscopy.

Results

Inhalation of 67% H₂ improved the 7-day survival rates and recognition memory function of septic mice, alleviated brain antioxidant enzyme activity (SOD and CAT), and reduced serum proinflammatory cytokine levels. H₂ inhalation also enhanced the expression of MFN2 and mitochondrial biogenesis-related factors (PGC-1α, NRF2, and TFAM) and decreased the expression of fission protein (DRP1), leading to improvement in mitochondrial function, as evidenced by MMP and ATP levels.

Conclusions

Inhalation of high concentration (67%) of H₂ in septic mice improved the survival rate and reduced neuronal injury. Its mechanism might be mediated by enhancing mitochondrial biogenesis and mitochondrial dynamics.

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高浓度氢气吸入可通过改善线粒体动力学缓解小鼠败血症相关脑病

背景败血症相关脑病（SAE）是一种预后不良的神经元损伤。线粒体功能障碍是 SAE 发生的关键因素，而氢气（H2）对脓毒症小鼠有保护作用。本研究旨在探讨高浓度（67%）氢气对 SAE 的影响，以及这种影响是否与线粒体生物生成和线粒体动力学有关。方法通过盲肠结扎和穿刺诱导小鼠败血症模型。小鼠分别在术后 1 小时和 6 小时吸入 67% 的 H2 1 小时。记录小鼠的 7 天存活率。认知功能采用Y迷宫测试和莫里斯水迷宫测试进行评估。术后24小时评估血清炎症因子、抗氧化酶以及线粒体功能指标，包括海马组织中的线粒体膜电位（MMP）和ATP。检测了海马组织中的线粒体动态蛋白（DRP1和MFN2）和生物合成蛋白（PGC-1α、NRF2和TFAM）。此外，还通过透射电子显微镜观察了线粒体的形态。结果吸入 67% 的 H2 提高了败血症小鼠的 7 天存活率和识别记忆功能，减轻了脑部抗氧化酶活性（SOD 和 CAT），降低了血清促炎细胞因子水平。吸入 H2 还可提高 MFN2 和线粒体生物生成相关因子（PGC-1α、NRF2 和 TFAM）的表达，降低裂变蛋白（DRP1）的表达，从而改善线粒体功能，这一点可从 MMP 和 ATP 水平得到证明。结论对脓毒症小鼠吸入高浓度（67%）的 H2 可提高存活率并减少神经元损伤。其机制可能是通过增强线粒体生物生成和线粒体动力学来实现的。

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

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.