Hydrogen Gas Protects Brain Function During Sepsis in Mice
- Authors
- Jianfeng Liu, Shuqi Meng, Zhiwei Wang, Yan Fan, Shuaijie Pei, Jiatian Cui, Jie Liu, Yu Song, Xiaofan Huang, Xuguang Li, Yan Cui, Keliang Xie
- Journal
- European Journal of Medical Research
- Year
- 2025
- DOI
- 10.1186/s40001-025-03600-5
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Sepsis-Associated Encephalopathy
- Body System
- Nervous System
TL;DR
Hydrogen inhalation improved survival and protected brain function in sepsis by activating mitochondrial repair and reducing inflammation.
Key Finding
Inhaling 2% hydrogen gas increased survival in septic mice from 50% to 75% and improved cognitive performance, with these benefits appearing to depend on activation of the SIRT1 protein.
Summary
This mouse study investigated how molecular hydrogen gas might protect the brain during sepsis (a life-threatening infection). Researchers exposed septic mice to 2% hydrogen gas and found it improved survival rates, enhanced memory and learning ability, and reduced brain inflammation and cell death. The protective effect appeared to work by activating a protein called SIRT1, which helped cells clean up damaged mitochondria (the energy-producing structures inside cells).
Practical Takeaway
While this is early-stage research in mice only, it suggests hydrogen gas inhalation may have neuroprotective potential in sepsis-related brain dysfunction. However, this is a single animal study with an unknown sample size and duration, so results cannot yet be applied to humans. Clinical trials would be needed before any therapeutic claims could be made.
Abstract
Background: Sepsis-associated encephalopathy (SAE) constitutes a major determinant of sepsis-related mortality across acute and survivorship phases. While molecular hydrogen (H₂) exhibits neuroprotective capacities in SAE, its precise mechanistic underpinnings remain unresolved. This study investigates the protection of SAE by H2 through regulating SIRT1-mediated mitophagy. Methods: SAE was modeled in mice via cecal ligation and puncture (CLP). The cognitive abilities of mice were evaluated via behavioral tests (Morris water maze), observation of the pathological morphology of brain tissues (HE staining), and observation of neuronal cell structure (Nissl staining). Proteomics was employed to explore the specific mechanism by which hydrogen regulates mitophagy. Western blotting, immunofluorescence, and electron microscopy were used to quantify the dynamic changes of sirtuin 1 (SIRT1) and mitophagy during SAE. In addition, an SIRT1 inhibitor (EX527) was utilized to observe its effects on hydrogen treatment and mitophagy. Results: Inhalation of 2% hydrogen significantly enhanced the 7-day survival rate of septic mice (from 50 to 75%, P < 0.01) and improved cognitive performance in the Morris water maze, as evidenced by increased platform crossings (P < 0.05) and reduced escape latency. Hydrogen treatment upregulated SIRT1 expression and promoted PINK1/Parkin-mediated mitophagy, leading to reduced phosphorylation of STING, decreased levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), and suppressed neuronal apoptosis in the hippocampal CA1 region. These protective effects were reversed by the SIRT1 inhibitor EX527. Conclusions: This study demonstrates that inhalation of 2% H2 exerts significant protective effects against SAE, in which SIRT1 plays a pivotal role by modulating PINK1-dependent mitophagy, thereby ameliorating neuroinflammation and neuronal apoptosis. By rescuing mitophagy deficits, SIRT1 targeting merits clinical exploration for SAE.