Hydrogen Therapy Protects Brain in Sepsis Study
- Authors
- John Sieh Dumbuya, Xinxin Chen, Jiang Du, Siqi Li, Lili Liang, Hairui Xie, Qiyi Zeng
- Journal
- International Immunopharmacology
- Year
- 2023
- DOI
- 10.1016/j.intimp.2023.110758
- Study Type
- Rat
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Sepsis-Associated Encephalopathy
- Body System
- Nervous System
TL;DR
Hydrogen-rich saline may help protect the brains of young rats from the harmful effects of sepsis.
Key Finding
Hydrogen-rich saline reduced brain inflammation and neuronal damage in septic rats by suppressing NLRP3 inflammasome activation (a cellular trigger for inflammation) and enhancing antioxidant enzyme activity.
Summary
This study tested hydrogen-rich saline (a salt solution containing dissolved hydrogen gas) in rats with sepsis-associated encephalopathy, a brain condition that can develop during severe infections. Researchers found that the hydrogen-rich saline reduced brain inflammation, decreased markers of cellular damage, and boosted the rats' natural antioxidant defenses (molecules that protect cells from damage). The treatment appeared to work by blocking a specific inflammatory pathway in the brain.
Practical Takeaway
While these results are promising, this was a rat study only and does not directly translate to humans. Early evidence suggests hydrogen-rich saline may have neuroprotective potential in sepsis-related brain injury, but human clinical trials would be needed to determine whether it could be effective and safe as a treatment for sepsis-associated encephalopathy in patients.
Abstract
Sepsis-associated encephalopathy (SAE) is characterised by long-term cognitive impairment and psychiatric illness in sepsis survivors, associated with increased morbidity and mortality. There is a lack of effective therapeutics for SAE. Molecular hydrogen (H2) plays multiple roles in septic diseases by regulating neuroinflammation, reducing oxidative stress parameters, regulating signalling pathways, improving mitochondrial dysfunction, and regulating astrocyte and microglia activation. Here we report the protective effect of hydrogen-rich saline in the juvenile SAE rat model and its possible underlying mechanisms. Rats were injected intraperitoneally with lipopolysaccharide at a dose of 5 mg/kg to induce sepsis; Hydrogen-rich saline (HRS) was administered 1 h after LPS induction at a dose of 5 ml/kg and nigericin at 1 mg/kg 1 h before LPS injection. H&E staining for neuronal damage, TUNEL assay for detection of apoptotic cells, immunofluorescence, ELISA protocol for inflammatory cytokines and 8-OHdG determination and western blot analysis to determine the effect of HRS in LPS-induced septic rats. Rats treated with HRS showed decreased TNF-α and IL-1β expression levels. HRS treatment enhanced the activities of antioxidant enzymes (SOD, CAT and GPX) and decreased MDA and MPO activities. The number of MMP-9 and NLRP3 positive immunoreactivity cells decreased in the HRS-treated group. Subsequently, GFAP, IBA-1 and CD86 immunoreactivity were reduced, and CD206 increased after HRS treatment. 8-OHdG expression was decreased in the HRS-treated rats. Western blot analysis showed decreased NLRP3, ASC, caspase-1, MMP-2/9, TLR4 and Bax protein levels after HRS treatment, while Bcl-2 expression increased after HRS treatment. These data demonstrated that HRS attenuated neuroinflammation, NLRP3 inflammasome activation, neuronal injury, and mitochondrial damage via NLRP3/Caspase-1/TLR4 signalling in the juvenile rat model, making it a potential therapeutic agent in the treatment of paediatric SAE.