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Background: The optimal timing of hyperbaric oxygen (HBO2) treatments for the best recovery following muscle injury has yet to be determined. Thus, the optimal number and timing of HBO2 treatments for maximal muscle regeneration were explored., Methods: The HBO2 treatment protocol consisted of 2.5 ATA 100% oxygen for 120 minutes. Muscle-injured rats were randomized to one of 10 groups: single HBO2 treatment immediately after injury (HBO 1T day 0), one day (HBO 1T day 1), three days (HBO 1T day 3) and five days (HBO 1T day 5) after injury; three HBO2 treatments from immediately after injury to two days after injury (HBO 3T day 0-2), from one to three days after injury (HBO 3T day 1-3), from three to five days after injury (HBO 3T day 3-5), from five to seven days after injury (HBO 3T day 5-7); five daily HBO2 treatments (HBO 5T); and no treatment (NT)., Results: HBO 5T and HBO 3T day 0-2, days 1-3 and days 3-5 significantly promoted CD206-positive cell infiltration, satellite cell differentiation and muscle regeneration compared to the NT group., Conclusion: Five HBO2 treatments and three HBO2 treatments within three days of injury promote muscle regeneration., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Hyperbaric oxygen (HBO) treatment promotes early recovery from muscle injury. Reactive oxygen species (ROS) upregulation is a key mechanism of HBO, which produces high O 2 content in tissues through increased dissolution of oxygen at high pressure. Nitric oxide (NO), a type of ROS, generally stabilizes hypoxia-inducible factor (HIF) 1α and stimulates secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) from endothelial cells and macrophages, which then induces angiogenesis. The purpose of the present study was to investigate whether HBO could promote angiogenesis via induction of NO and induce muscle regeneration in contused rat skeletal muscles. The HBO protocol consisted of 2.5 atmospheres absolute (ATA) 100% oxygen for 120 minutes, once a day for 5 consecutive days. We also evaluated the effects of a ROS inhibitor (NAC) or NOS-specific inhibitor (L-NAME) on HBO. HBO significantly increased NO 3 - , VEGF, and bFGF levels and stabilized HIF1α within 1 day. HBO promoted blood vessel formation at 3-7 days and muscle healing at 5-7 days after contusion. Administration of both NAC and L-NAME before HBO suppressed angiogenesis and muscle regeneration even after HBO. HBO thus promoted angiogenesis and muscle regeneration mainly through generation of NO in the early phase after muscle contusion injury.

Hyperbaric oxygen treatment (HBO) promotes rapid recovery from soft tissue injuries. However, the healing mechanism is unclear. Here we assessed the effects of HBO on contused calf muscles in a rat skeletal muscle injury model. An experimental HBO chamber was developed and rats were treated with 100% oxygen, 2.5 atmospheres absolute for 2 h/day after injury. HBO reduced early lower limb volume and muscle wet weight in contused muscles, and promoted muscle isometric strength 7 days after injury. HBO suppressed the elevation of circulating macrophages in the acute phase and then accelerated macrophage invasion into the contused muscle. This environment also increased the number of proliferating and differentiating satellite cells and the amount of regenerated muscle fibers. In the early phase after injury, HBO stimulated the IL-6/STAT3 pathway in contused muscles. Our results demonstrate that HBO has a dual role in decreasing inflammation and accelerating myogenesis in muscle contusion injuries.

Sulforaphane (SFN) plays an important role in preventing oxidative stress by activating the nuclear factor (erythroid derived 2)-like 2 (Nrf2) signalling pathway. SFN may improve exercise endurance capacity by counteracting oxidative stress-induced damage during exercise. We assessed running ability based on an exhaustive treadmill test (progressive-continuous all-out) and examined the expression of markers for oxidative stress and muscle damage. Twelve- to 13-week-old Male wild-type mice (Nrf2 +/+ ) and Nrf2-null mice (Nrf2 -/- ) on C57BL/6J background were intraperitoneally injected with SFN or vehicle prior to the test. The running distance of SFN-injected Nrf2 +/+ mice was significantly greater compared with that of uninjected mice. Enhanced running capacity was accompanied by upregulation of Nrf2 signalling and downstream genes. Marker of oxidative stress in SFN-injected Nrf2 +/+ mice were lower than those in uninjected mice following the test. SFN produced greater protection against muscle damage during exhaustive exercise conditions in Nrf2 +/+ mice than in Nrf2 -/- mice. SFN-induced Nrf2 upregulation, and its antioxidative effects, might play critical roles in attenuating muscle fatigue via reduction of oxidative stress caused by exhaustive exercise. This in turn leads to enhanced exercise endurance capacity. These results provide new insights into SFN-induced upregulation of Nrf2 and its role in improving exercise performance.

Regular physical exercise is central to a healthy lifestyle. However, exercise-related muscle contraction can induce reactive oxygen species and reactive nitrogen species (ROS/RNS) production in skeletal muscle. The nuclear factor-E2-related factor-2 (Nrf2) transcription factor is a cellular sensor for oxidative stress. Regulation of nuclear Nrf2 signaling regulates antioxidant responses and protects organ structure and function. However, the role of Nrf2 in exercise- or contraction-induced ROS/RNS production in skeletal muscle is not clear. In this study, using differentiated C2C12 cells and electrical pulse stimulation (EPS) of muscle contraction, we explored whether Nrf2 plays a role in the skeletal muscle response to muscle contraction-induced ROS/RNS. We found that EPS (40 V, 1 Hz, 2 ms) stimulated ROS/RNS accumulation and Nrf2 activation. We also showed that expression of NQO1, HO-1 and GCLM increased after EPS-induced muscle contraction and was remarkably suppressed in cells with Nrf2 knockdown. We also found that the antioxidant N-acetylcysteine (NAC) significantly attenuated Nrf2 activation after EPS, whereas the nitric oxide synthetase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) did not. Furthermore, Nrf2 knockdown after EPS markedly decreased ROS/RNS redox potential and cell viability and increased expression of the apoptosis marker Annexin V in C2C12 myotubes. These results indicate that Nrf2 activation and expression of Nrf2 regulated-genes protected muscle against the increased ROS caused by EPS-induced muscle contraction. Thus, our findings suggest that Nrf2 may be a key factor for preservation of muscle function during muscle contraction.

The purpose of this study was to investigate the effects of hyperbaric oxygen (HBO) treatment on muscle fatigue after maximal intermittent plantar flexion exercise. Twenty healthy male volunteers (aged from 21 to 24 years) were randomly assigned to either HBO or normoxic group and were blinded to their treatment and group assignment. The HBO group breathed 100% oxygen under 2.5 atmosphere absolute (ATA) for 60 minutes, whereas the normoxic group breathed room air under 1.2 ATA for 70 minutes. The subjects performed a fatigue test, which consisted of 50 maximal unilateral isometric plantar flexions, before and after intervention. Surface electromyography was recorded from triceps surae muscle. Subjects performed maximal voluntary contractions of isometric plantar flexions, and voluntary activation and twitch contractile properties were evaluated with cutaneous tibial nerve stimuli before and after intervention. Compared with initial values during repetitions 4-10, the plantar flexion torque during repetitions 41-50 decreased to 88.5 and 83.2% after HBO and normoxic treatment, respectively. A smaller decrease in muscle force was observed in the HBO group compared with the normoxic group. No differences in function between treatment groups were observed after nerve stimulation. These results suggest that HBO contributes to sustained force production due to suppressing the muscle fatigue progression. In practice, HBO can contribute to the prevention of excess fatigue of agonist muscles for specific exercises involving repeated jumping.