Neuroprotection under pressure: rethinking hyperbaric oxygen therapy

This Perspective explores why hyperbaric oxygen therapy (HBOT) deserves closer clinical and scientific attention as a possible treatment for ischemic stroke and a potential neuroprotective strategy in chronic central nervous system disorders, especially multiple sclerosis and other progressive or age-related neurological conditions. While HBOT is not yet widely accepted for these indications, three factors justify reconsideration: its strong safety profile, a biologically plausible mechanistic rationale, and recurrent signals of benefit from selected neurological studies. We review HBOT’s historical development, current accepted indications, and evidence that adverse effects are generally mild, uncommon, and reversible under modern protocols. In neurology, efficacy remains unproven, yet interest persists due to preliminary findings and repeated patient-reported improvements. A central argument is that the main barrier to progress is not safety, but evidence generation. Conventional randomized controlled trials face major challenges: difficult blinding, wide variation in dosing protocols, and uncertainty about meaningful outcomes in chronic neurological disease. Moreover, HBOT is non-patentable, which limits commercial investment and leaves a potentially valuable intervention underexplored. Mechanistically, we move beyond explanations centred solely on oxygen delivery or oxidative stress. As a working hypothesis, neurological benefits may partly arise from cumulative adaptive responses—including a rebound hormesis following repeated hyperoxic exposure. We conclude with a pragmatic research agenda: continuous, low-cost physiological monitoring in patients already receiving HBOT, coupled with a medium-term goal of adequately powered efficacy trials.