Hydrogen Gas Protects Brain After Stroke by Repairing Cell Powerhouses
- Authors
- Jiatong Zhang, Yan Zhou, Xiaolong Zhu, Zheng Peng, Qi Zhu, Pengfei Ding, Mingzhe Ning, Qing-Rong Zhang, Zong Zhuang
- Journal
- Antioxidants & Redox Signaling
- Year
- 2025
- DOI
- 10.1177/15230864251410952
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Subarachnoid Hemorrhage
- Body System
- Nervous System
TL;DR
Hydrogen protected the brain after hemorrhage by improving mitochondrial health and activating cellular antioxidant defense pathways.
Key Finding
Hydrogen gas inhalation activated a specific molecular pathway (NRF2-PINK1/Parkin) that enhanced the brain's ability to remove damaged mitochondria and reduce oxidative stress after subarachnoid hemorrhage in mouse models.
Summary
This study investigated how hydrogen gas might protect the brain after a specific type of stroke called subarachnoid hemorrhage. Using mouse models and laboratory cell cultures, researchers found that inhaling hydrogen gas improved neurological function and reduced cellular damage caused by harmful molecules called free radicals. The protection worked by activating a cleanup system inside cells' energy-producing structures (mitochondria) that removes damaged parts, triggered by a protein called NRF2.
Practical Takeaway
While this study identifies a promising mechanism for how hydrogen might protect brain tissue after hemorrhagic stroke, it was conducted only in mice and laboratory cells—not in humans. The findings suggest hydrogen warrants further investigation as a potential treatment, but much more research, including human clinical trials, would be needed before any health claims could be made.
Abstract
Aims: Mitochondrial dysfunction is recognized as a central pathological mechanism in subarachnoid hemorrhage (SAH). This study aimed to investigate whether mitophagy serves as a key mechanism by which hydrogen (H2) exerts its antioxidative effects following SAH. Results: Using in vivo (mouse SAH model) and in vitro (HT22 cell SAH model) approaches, we demonstrated that H2 inhalation significantly improved neurological function and alleviated oxidative stress and apoptosis. Mechanistically, H2 maintained mitochondrial membrane potential and functional integrity by enhancing phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy. RNA sequencing and functional assays identified nuclear factor erythroid 2-related factor 2 (NRF2) as the key upstream target. H2 promoted NRF2 nuclear translocation and activated the antioxidant pathway. Dual-luciferase reporter assays further confirmed that NRF2 directly binds to and activates the PINK1 promoter. Pharmacological inhibition of NRF2 (ML385) or mitophagy (Mdivi-1) abolished the protective effects of H2, confirming that the NRF2-PINK1/Parkin axis is central to the effect of H2. Innovation: The present study clearly establishes the NRF2-PINK1/Parkin axis as a key mechanism underlying the neuroprotective effect of H2 in SAH. This study connects mitochondrial quality control with endogenous antioxidant systems, suggesting H2 administration as a potential mitochondrion-targeted clinical intervention. Conclusion: The NRF2-PINK1/Parkin axis is a novel and key mechanism underlying the neuroprotective effect of H2 in SAH. This finding advances our understanding beyond general antioxidant theories by demonstrating a specific, multistep molecular cascade. H2 administration is a potential mitochondrion-targeted intervention with strong implications for clinical translation in SAH patients. Antioxid. Redox Signal. 00, 000-000.