Hydrogen Gas Reduces Brain Damage from Stroke in Mice Study
- Authors
- Zhenkui Wang, Wei Feng, Jie Zhou, Lei Huang, Chuanfeng Fang, Jiarong Yuan, Hongsheng Chen, Li Xue
- Journal
- Journal of Stroke and Cerebrovascular Diseases
- Year
- 2026
- DOI
- 10.1016/j.jstrokecerebrovasdis.2026.108645
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Stroke
- Body System
- Nervous System
TL;DR
Hydrogen inhalation reduced brain injury after cerebral ischemia-reperfusion in mice and protected oxygen-glucose-deprived neuronal cells by improving mitochondrial function, reducing oxidative stress and apoptosis, and activating Nrf2/PINK1/Parkin-mediated mitophagy.
Key Finding
Hydrogen gas inhalation reduced stroke-induced brain damage in mice and protected brain cells in laboratory studies by activating a cellular cleanup process (mitophagy) that removes damaged mitochondria.
Summary
This study tested whether hydrogen gas could protect brain cells from damage that occurs after a stroke. Researchers used mice with induced strokes and brain cells in lab dishes exposed to oxygen deprivation (mimicking stroke conditions). They found that hydrogen gas treatment reduced brain damage, improved neurological function in mice, and protected cells by activating a cleanup process called mitophagy (where cells remove damaged mitochondria, which are the cell's energy-producing structures). The protection appeared to work through specific molecular pathways that reduce harmful oxidative stress and prevent cell death.
Practical Takeaway
This early-stage research in mice and lab cells suggests hydrogen gas may have neuroprotective potential for stroke injury, but it is not yet tested in humans. The study identifies specific molecular mechanisms that may explain how hydrogen works, which could guide future clinical research. However, much more work—including human trials—would be needed before hydrogen could be considered a proven stroke treatment.
Abstract
Background: Cerebral ischemia-reperfusion injury (CIRI) causes severe neuronal damage following restoration of cerebral blood flow, and mitochondrial dysfunction acts as a core pathological driver of this process. Molecular hydrogen (H₂) has exhibited promising neuroprotective effects in multiple neurological disease models, yet it remains unclear whether H2 alleviates CIRI by modulating mitophagy and its upstream regulatory signaling pathways. Methods: In vivo experiments were performed using male C57BL/6 mice subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) with mice randomly divided into three groups: Sham group, MCAO/R group, and MCAO/H₂ group. In vitro, human neuroblastoma SH-SY5Y cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), with four experimental groups: Control group, OGD/R group, OGD/R+H₂ group, and OGD/R+H₂+ML385 group (5 μM ML385, a specific Nrf2 inhibitor, pretreated for 1h before OGD). Neurological function was assessed via neurological deficits score (zea-Longa); cerebral infarct volume was measured by TTC staining; neuronal histopathological damage and apoptosis were evaluated via HE, Nissl, and TUNEL staining; cell viability was detected using CCK-8 assay; cell apoptosis, mitochondrial reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) were analyzed by flow cytometry; protein expression levels were quantified by Western blotting. Results: In vivo experiments demonstrated that H₂ inhalation markedly alleviated neurological deficits, reduced cerebral infarct volume and histopathological damage, inhibited neuronal apoptosis, and promoted mitophagy in MCAO/R mice. In SH-SY5Y cells, H₂ treatment significantly improved cell viability, attenuated oxidative stress and mitochondrial dysfunction, and enhanced mitophagy via activation of the PINK1/Parkin pathway. Mechanistically, H₂ maintained cellular redox homeostasis, cleared damaged mitochondria, upregulated the Nrf2/HO-1 antioxidant pathway, and suppressed NF-κB-mediated inflammatory signaling. Notably, inhibition of Nrf2 with ML385 significantly reversed the mitochondrial protective and anti-apoptotic effects of H₂ in OGD/R-exposed cells. Conclusion: Our findings revealed that H2 exerts significant neuroprotective effects against CIRI by attenuating oxidative stress, inhibiting neuronal apoptosis, and improving mitochondrial function. These effects are closely associated with the activation of the Nrf2/PINK1/Parkin-mediated mitophagy pathway, highlighting H₂ as a potential therapeutic method for CIRI.