Mitochondrial dysfunction, neuroinflammation, and associated mechanisms in sepsis-associated encephalopathy: from pathogenesis to emerging therapeutics.
Yong Shen, Xue-Mei Ye, Ping-Yang Li, Si-Lei Chen · Frontiers in neuroscience · 2026
Research-use notice
Independent study record
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H2HUBB TAKEAWAY
This narrative review examined the available molecular-hydrogen literature. Sepsis-associated encephalopathy (SAE) is a devastating neurological complication of sepsis, leading to diffuse brain dysfunction, long-term cognitive deficits, and increased mortality. The reviewed evidence adds support for molecular hydrogen's therapeutic potential across the conditions, mechanisms, or outcomes examined.
What the Findings Mean
H2HUBB reviewed this publication as a synthesis of molecular-hydrogen research and summarizes the outcomes emphasized by the authors. Sepsis-associated encephalopathy (SAE) is a devastating neurological complication of sepsis, leading to diffuse brain dysfunction, long-term cognitive deficits, and increased mortality.
What the Researchers Studied
The authors reviewed mitochondrial dysfunction, neuroinflammation, and associated mechanisms in sepsis-associated encephalopathy: from pathogenesis to emerging therapeutics.
What Effects Did Molecular Hydrogen Have?
Sepsis-associated encephalopathy (SAE) is a devastating neurological complication of sepsis, leading to diffuse brain dysfunction, long-term cognitive deficits, and increased mortality. The core findings can be summarized as follows: (1) mitochondrial dynamics are profoundly disrupted in SAE, with excessive Drp1-mediated fission and impaired fusion leading to bioenergetic failure, oxidative stress, and activation of mitochondria-dependent cell death pathways (apoptosis, pyroptosis, ferroptosis). (2) microglial activation, particularly through the NLRP3 inflammasome, creates a self-perpetuating cycle of neuroinflammation that exacerbates mitochondrial damage and synaptic loss. (3) BBB disruption, driven by endothelial mitochondrial dysfunction and tight junction disassembly, facilitates the entry of neurotoxic mediators into the brain parenchyma; (4) the gut-brain axis and cerebral metabolomic alterations critically modulate mitochondrial function and inflammatory responses; and (5) emerging therapeutic strategies targeting this mitochondrial-neuroinflammatory axis—including molecular hydrogen, mitochondria-targeted peptides, natural compounds, and specific inhibitors—have demonstrated robust preclinical efficacy by restoring mitochondrial homeostasis and resolving neuroinflammation.
Why These Findings Matter
The reviewed evidence adds support for molecular hydrogen's therapeutic potential across the conditions, mechanisms, or outcomes examined.
How Strong Is This Evidence?
This is review or synthesis evidence (narrative review).
Technical Study Details
H2HUBB classifies this publication as narrative review with review or synthesis evidence. The study used a narrative review.
Limitations and Safety
No separate limitations or safety findings were identified in the current-study source text available to H2HUBB.
Original Study and H2HUBB Research Context
H2HUBB presents this source-grounded research record as one contribution to the broader molecular-hydrogen evidence base.