How Hydrogen Therapy May Help Brain Problems from Severe Infections
- Authors
- Yong Shen, Xue-Mei Ye, Ping-Yang Li, Si-Lei Chen
- Journal
- Frontiers in Neuroscience
- Year
- 2026
- DOI
- 10.3389/fnins.2026.1824178
- Study Type
- clinical
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Sepsis-Associated Encephalopathy
- Body System
- Nervous System
TL;DR
When people get really sick from severe infections (sepsis), their brain gets damaged because two problems happen at the same time: the tiny power plants inside brain cells break down, and the brain's immune system goes haywire and causes inflammation. Scientists found that if we can fix both of these problems at once using new treatments, we might be able to prevent brain damage and help people recover better.
Key Finding
Sepsis-associated brain damage involves a destructive cycle between mitochondrial dysfunction and neuroinflammation, with emerging evidence suggesting that molecular hydrogen and other mitochondria-targeted therapies may help break this cycle.
Summary
This review examines how sepsis (a life-threatening infection response) damages the brain by disrupting mitochondria (the cell's energy-producing structures) and triggering excessive inflammation. The authors explain how these two problems feed into each other, causing brain cell death and long-term cognitive problems, and they discuss emerging treatments—including molecular hydrogen—that may help by reducing both oxidative damage and inflammation.
Practical Takeaway
This is a review article summarizing existing research rather than a new study with results, and it does not include human trials. While the authors identify molecular hydrogen as a promising therapeutic candidate for sepsis-related brain injury, this conclusion is based on laboratory and animal research. Much more clinical evidence would be needed before hydrogen water could be considered a treatment for this serious condition.
Abstract
Sepsis-associated encephalopathy (SAE) is a devastating neurological complication of sepsis, leading to diffuse brain dysfunction, long-term cognitive deficits, and increased mortality. Its pathogenesis is complex, with mitochondrial dysfunction and neuroinflammation emerging as central, interconnected drivers. This review systematically elucidates the pathogenic crosstalk between these two processes. We detail how dysregulated mitochondrial dynamics (e.g., Drp1-mediated fission), impaired biogenesis (via the proliferator-activated receptor-gamma coactivator-1α axis), oxidative stress, and the activation of mitochondria-dependent cell death pathways (ferroptosis, pyroptosis) contribute to neuronal injury. Concurrently, microglial activation, particularly through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome, creates a vicious cycle that exacerbates mitochondrial damage and synaptic loss. Furthermore, we summarize emerging therapeutic strategies that target this mitochondrial-neuroinflammatory axis, including molecular hydrogen, mitochondria-targeted peptides (SS-31), natural compounds, and specific inhibitors (e.g., Mdivi-1, MCC950). The integration of recent insights on the gut-brain axis and cerebral metabolomics further expands the therapeutic landscape. Ultimately, targeting this core axis offers a promising paradigm for developing effective interventions to improve neurological outcomes in septic patients.