The protective effects of molecular hydrogen in sepsis-associated encephalopathy: current status

Sepsis-associated encephalopathy (SAE) is a severe neurological complication that arises in patients with sepsis, characterised by cognitive impairment and neurological dysfunction. Mechanisms contributing to SAE include oxidative stress, inflammation, mitochondrial dysfunction, and blood-brain barrier disruption. Recent studies indicate that molecular hydrogen (H2) offers therapeutic benefits for SAE due to its antioxidant and anti-inflammatory properties. H2 therapy has shown promise in alleviating oxidative stress, neuroinflammation, and neuronal damage linked to SAE, primarily through scavenging reactive oxygen species, suppressing astrocyte and microglia activation, and mitigating mitochondrial dysfunction. However, variations in treatment protocols (such as dosage, delivery methods, and administration routes) limit the generalizability of findings. Despite these challenges, H2 therapy is well-tolerated with minimal adverse effects. This review synthesises the current evidence on H2 therapy in SAE and highlights key directions for future research, focusing on standardising protocols, optimising treatment regimens, and investigating long-term impacts.