Hydrogen Therapy Protects Brain Function During Sepsis in Mice
- Authors
- Yuanyuan Bai, Wen Mi, Xiaoyin Meng, Beibei Dong, Yi Jiang, Yuechun Lu, Yonghao Yu
- Journal
- BMC Neuroscience
- Year
- 2023
- DOI
- 10.1186/s12868-023-00795-3
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Sepsis-Associated Encephalopathy
- Body System
- Nervous System
TL;DR
Hydrogen gas treatment improves survival and brain function in mice with sepsis by reducing inflammation and protecting the brain's protective barrier, possibly through a mechanism involving PPARα and certain cellular transporters.
Key Finding
Hydrogen gas improved survival rates and cognitive function in mice with sepsis-associated brain dysfunction by protecting the blood-brain barrier through a mechanism involving PPARα activation and regulation of cellular transport proteins.
Summary
This study investigated how hydrogen gas might protect the brain during sepsis (a life-threatening infection response). Researchers used mice with sepsis-like conditions and found that hydrogen gas improved survival rates, preserved brain function (tested through memory and learning tasks), and protected the blood-brain barrier—a protective membrane that controls what enters the brain. The protection appeared to work by activating a protein called PPARα, which then regulated other proteins responsible for removing harmful substances from the brain.
Practical Takeaway
While this mouse study suggests hydrogen gas may have protective effects on the brain during severe infection, it is early-stage research that has not been tested in humans. The findings are promising for understanding potential mechanisms, but much more research—including human trials—would be needed before hydrogen could be considered a treatment for sepsis-related brain complications.
Abstract
Hydrogen (H2) can protect against blood‒brain barrier (BBB) damage in sepsis-associated encephalopathy (SAE), but the mechanism is still unclear. We examined whether it is related to PPARα and its regulatory targets, ABC efflux transporters. After injection with DMSO/GW6471 (a PPARα inhibitor), the mice subjected to sham/caecal ligation and puncture (CLP) surgery were treated with H2 for 60 min postoperation. Additionally, bEnd.3 cells were grown in DMSO/GW6471-containing or saline medium with LPS. In addition to the survival rates, cognitive function was assessed using the Y-maze and fear conditioning tests. Brain tissues were stained with TUNEL and Nissl staining. Additionally, inflammatory mediators (TNF-α, IL-6, HMGB1, and IL-1β) were evaluated with ELISA, and PPARα, ZO-1, occludin, VE-cadherin, P-gp, BCRP and MRP2 were detected using Western blotting. BBB destruction was assessed by brain water content and Evans blue (EB) extravasation. Finally, we found that H2 improved survival rates and brain dysfunction and decreased inflammatory cytokines. Furthermore, H2 decreased water content in the brain and EB extravasation and increased ZO-1, occludin, VE-cadherin and ABC efflux transporters regulated by PPARα. Thus, we concluded that H2 decreases BBB permeability to protect against brain dysfunction in sepsis; this effect is mediated by PPARα and its regulation of ABC efflux transporters.