Hyperbaric oxygen therapy for fatigue recovery: Experimental evidence and optimal regimen from a mouse model established by a chronic multi-stressor paradigm.

Abstract

AIMS: Fatigue in safety-critical occupations is multifactorial and often overlaps with chronic stress-related neurobehavioral impairment. Hyperbaric oxygen therapy (HBOT) may accelerate fatigue recovery, but its efficacy and optimal regimen are unclear. We evaluated HBOT and identified the optimal number of sessions in a mouse chronic multi-stressor-induced fatigue-like phenotype. MATERIALS AND METHODS: C57BL/6 J mice subjected to a multi-stressor paradigm (restraint, noise, forced running, and overcrowding for 15 days) underwent different post-fatigue interventions: natural recovery, normobaric oxygen (NBO, 100% Oat 1 ATA, 60 min/session/day), or HBOT(100% Oat 2.5 ATA, 60 min/session/day) for 3 days respectively. In parallel, different HBOT frequencies (1, 3, 7, or 14 consecutive days of once-daily HBOT) were compared. Outcomes included physical endurance, cognitive function, mood-related behaviors, biochemical indicators of stress, inflammation and oxidative damage, and histopathology of liver and hippocampus. KEY FINDINGS: Within 3 days, natural rest produced limited improvement and NBO provided only marginal gains. In contrast, HBOT yielded significant improvements in physical, cognitive, and emotional outcomes. Among HBOT regimens, 3 and 7 sessions achieved near-complete recovery across multiple indices, whereas 1 session was insufficient. Fourteen sessions conferred no additional benefit and several readouts suggested attenuation of the early advantage. SIGNIFICANCE: HBOT provides a rapid, short-course intervention that accelerates recovery in this multi-stressor fatigue-like model. A 3-7 session regimen (2.5 ATA, 60 min each) appears sufficient across functional and biological endpoints, supporting further translational evaluation of time-efficient HBOT protocols while avoiding unnecessary prolonged exposure.