Hydrogen Gas Protects Brain from Sepsis Damage in Mice Study
- Authors
- Yuanyuan Bai, Zeyu Li, Donglai Yan, Yi Jiang, Beibei Dong, Yonghao Yu
- Journal
- Brain and Behavior
- Year
- 2025
- DOI
- 10.1002/brb3.70761
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Sepsis-Associated Encephalopathy
- Body System
- Nervous System
TL;DR
Hydrogen gas protected the brains of septic mice by restoring lipid balance and reducing inflammation-related damage.
Key Finding
Hydrogen gas inhalation reduced brain damage in septic mice by lowering levels of a protein called DGKζ, which helped rebalance fat-like molecules (DAG and PA) in brain cells.
Summary
This study used mice with sepsis (a life-threatening infection) to investigate how inhaling hydrogen gas might protect the brain from damage. Researchers analyzed thousands of molecules and proteins in the mice's brains and found that hydrogen inhalation changed the activity of specific proteins involved in fat metabolism, particularly one called DGKζ. These changes appeared to reduce brain inflammation and damage in the septic mice.
Practical Takeaway
While this mouse study suggests hydrogen gas may have protective effects on the brain during severe infection, it is a preliminary animal study and does not directly demonstrate effects in humans. Much more research, including human trials, would be needed before any health recommendations could be made based on these findings.
Abstract
Objectives: Therapeutic effects of hydrogen (H2) on sepsis-associated encephalopathy (SAE), a severe neuroinflammatory disease, have been reported, but the underlying mechanism remains unclear. Metabolomic and phosphoproteomic analyses were utilized to explore the therapeutic mechanism of H2. Methods: Caecal ligation and puncture (CLP) was used to establish an animal model of sepsis, after which the animals were treated with hydrogen. Mouse brains were obtained for analysis via tandem mass tag-based quantitative proteomics with IMAC enrichment of phosphopeptides and LC-MS/MS analysis to provide a broad overview of the metabolites. The metabolic profiles of mice in the SAE and SAE + H2 groups were compared by multivariate statistical analysis. Different proteins (or enzymes) were verified by western blot (WB) and immunofluorescence (IF) analyses. ELISA was used to measure the level of DAG and PA. The influence of diacylglycerol kinase ζ (DGKζ) on glycerophospholipid metabolism in the mouse hippocampus was analyzed via coimmunoprecipitation (co-IP), and protein‒protein interactions were detected via LC‒MS/MS analysis. Results: A total of 1476 metabolites were identified, including 131 metabolic biomarkers in negative ion mode and 41 metabolic biomarkers in positive ion mode. These values were different from the standard, with variable importance for the projection (VIP) > 1 and p < 0.05. The correlated differential phosphoproteins found in the combined metabolomic and phosphoproteomic analyses participated in 131 pathways, and the differentially abundant metabolites were involved in 10 metabolic pathways, eight of which were related. The roles and interactions of these differentially expressed proteins and metabolites suggest that glycerophospholipid metabolism is activated in septic mice after the inhalation of hydrogen. Additionally, we quantified the downregulation of choline-phosphate cytidylyltransferase A (Pcyt1α)/CTP/CCTα and DGKζ and the upregulation of the metabolite sn-glycero-3-phosphoethanolamine in the glycerophospholipid metabolism pathway in mice in the SAE + H2 group compared with mice in the SAE group. The WB and IF results revealed that DGKζ expression increased in septic mice but decreased after H2 treatment. The ELISA showed that the expression of DAG was increased in SAE mice compared with Sham mice, while it decreased in SAE + H2 mice compared with SAE mice. Correspondingly, the PA level was reduced in SAE group compared with Sham group and was increased after the inhalation of H2. Furthermore, the regulation of DGKζ in hydrogen treatment in septic mice may be related to the interaction with phosphatase and tensin homolog (PTEN). Conclusion: H2 downregulates the levels of DGKζ and CCTα to alleviate brain damage in septic mice, and changes in DGKζ expression are balancing the transformation between the DAG anf PA, and it might also interact with PTEN. Thus, DGKζ may be a potential target in septic mouse therapy.