Anti-Aging

To test the protective properties of hyperbaric oxygen (HBO) on a tissue level, we evaluated the ability of a preconditioning treatment regimen to protect cutaneous tissue from UV-A-induced oxidative damage. Three groups of hairless SKH1-E mice were exposed to UV-A 3 days per week for 22 weeks, with two of these groups receiving an HBO pretreatment either two or four times per week. UV-A exposure increased apoptosis and proliferation of the skin tissue, indicating elevated levels of epithelial damage and repair. Pretreatment with HBO significantly reduced UV-A-induced apoptosis and proliferation. A morphometric analysis of microscopic tissue folds also showed a significant increase in skin creasing following UV-A exposure, which was prevented by HBO pretreatment. Likewise, skin elasticity was found to be greatest in the group treated with HBO four times per week. The effects of HBO were also apparent systemically as reductions in caspase-3 activity and expression were observed in the liver. Our findings support a protective function of HBO pretreatment from a direct oxidative challenge of UV-A to skin tissue. Similar protection of other tissues may likewise be achievable. Fuller et al. (2013) in "Hyperbaric oxygen preconditioning protects skin from UV-A damage"

The Fountain of Youth?
In the meantime, for all of us who have some degree of accelerated or premature aging, Hyperbaric Oxygen Therapy may in fact be an anti-aging tool. As Dr. Harch argues in The Oxygen Revolution, HBOT will likely become appreciated as the Fountain of Youth by the Baby Boomer Generation whose life spans have been compromised by years of drug experimentation in the 1960s and 1970s. Hyperbaric Oxygen Therapy will be able to restore waning brain function and prevent premature dementia.AltMd.com's "Hyperbaric Oxygen Therapy (HBOT) for Anti-Aging"

Although the underlying molecular causes of aging are not entirely clear, hormetic agents like exercise, heat, and calorie restriction may generate a mild pro-oxidant stress that induces cell protective responses to promote healthy aging. As an individual ages, many cellular and physiological processes decline, including wound healing and reparative angiogenesis. This is particularly critical in patients with chronic non-healing wounds who tend to be older. We are interested in the potential beneficial effects of hyperbaric oxygen as a mild hormetic stress on human microvascular endothelial cells. We analyzed global gene expression changes in human endothelial cells following a hyperbaric exposure comparable to a clinical treatment. Our analysis revealed an upregulation of antioxidant, cytoprotective, and immediate early genes. This increase coincided with an increased resistance to a lethal oxidative stress. Our data indicate that hyperbaric oxygen can induce protection against oxidative insults in endothelial cells and may provide an easily administered hormetic treatment to help promote healthy aging. Godman, et al. (2010) in "Hyperbaric oxygen treatment induces antioxidant gene expression"

Autism

Hyperbaric therapy is perhaps the safest procedure in medicine at the pressures used to treat brain injuries and children on the spectrum. K Paul Stoller, MD, FACHM, Chief of Hyperbaric Medicine Amen Clinics in Talk About Curing Autism's website

By increasing the amount of oxygen carried by the blood stream (more specifically, the plasma), the greater opportunity for oxygen deprived tissue to receive more oxygen.
Here's what I commonly see in my clinic:

• Improved sleep
• Improved bowel function
• Regulation of bowel movements
• Improved immune functioning with a decrease in frequent infections
• Improved expressive language
• Improved receptive language
• Improved fine and gross motor skills
• Improved muscle tone and strength
• Increased mental alertness
• Increased calmness
• Improved mood

Jerry Kartzinel, MD, FAAP, in Generation Rescue's blog

Children with autism who received hyperbaric treatment at 1.3 atm and 24% oxygen for 40 hourly sessions had significant improvements in overall functioning, receptive language, social interaction, eye contact, and sensory/cognitive awareness compared to children who received slightly pressurized room air. Rossignol, et al. (2009) in "BMC Pediatric's Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial"

Bone Repair

RESULTS: Autologous platelet concentrates (APC) and hyperbaric oxygen therapy (HBO), applied together or separately, increased the rate of bone healing compared with the control group.
Although there was no significant difference between the numbers of osteoblasts during any of the periods studied or between the number of osteocytes counted during the 2nd and 8th weeks, relative to the groups treated with APC and HBO combined, quantitative data on the average lesion thickness showed that the APCG, HBOG, and APC+HBOG were superior to the CG. The APC+HBOG was superior to the other groups across all periods, whereas the HBOG was superior to the APCG across all periods for this variable.
Most experimental studies have found a positive effect from HBO use in the fracture healing process. This effect may be directly associated with the increased formation of new vessels, which increases blood inflow and, thereby, bone formation.
We believe that the number of osteocytes associated with qualitative analysis and other variables, such as lesion thickness and percentage of collagen, better suggest the quantity of newly formed bone. In this study, APC+HBO was superior in producing a greater quantity of new bone compared with the APC, HBO, and control treatments during the 8th week. The importance of this study lies in the possibility of combining these two treatments, the effects of which potentiate increased bone formation. Additional studies with other variables must be conducted to deepen our knowledge of the effects of each of these treatments on bone healing; further studies should examine the economic impact of these combinations. The analysis of these outcomes allows us to state that APC and HBO combined increased the rate of bone healing in this experimental model. In addition, the rate of bone repair in the groups treated with APC or HBO were similar, and both rates were higher than in the CG. Neves, et al. (2013) in "Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing"

At week 2, defects treated with HBO exhibited greater numbers of cells positive for the endothelial marker CD31, up-regulated gene expression of osteogenic markers, and down-regulated expression of pro-inflammatory cytokines. At week 8, radiographic examination revealed that calvarial defects subjected to HBO exhibited a higher percentage of radiopacities than normobaric controls, and histological examination disclosed enhanced bone healing. These results confirmed that HBO treatment was effective in stimulating vascularization and bone formation in rat calvarial defects. Pedersen, et al. (2013) in "Hyperbaric oxygen stimulates vascularization and bone formation in rat calvarial defects."

Ultra-early stage hyperbaric oxygenation alleviates the hind limb bone loss in femur bone in rats following complete spinal cord transection. Liu, Wu, and Tong (2013) in "Effects of ultra-early stage hyperbaric oxygenation on the hind limb bone mineral density in rats after complete spinal cord transection."

We investigated whether the hyperbaric oxygen (O2) could promote the proliferation of growth-arrested osteoblasts in vitro and the mechanisms involved in this process. Osteoblasts were exposed to different combinations of saturation and pressure of O2 and evaluated at 3 and 7 days. . . Hyperbaric O2 significantly promoted osteoblast proliferation and cell cycle progression after 3 days of treatment. . . Our findings indicate that high pressure and high O2 saturation stimulates growth-arrested osteoblasts to proliferate. These findings suggest that the proliferative effects of hyperbaric O2 on osteoblasts may contribute to the recruitment of osteoblasts at the fracture site. Cheng-Pu Hsieh, Ya-Ling Chiou, and Ching-Yuang Lin (2010) in "Hyperbaric oxygen-stimulated proliferation and growth of osteoblasts may be mediated through the FGF-2/MEK/ERK 1/2/NF-κB and PKC/JNK pathways"

Brain Injury

Recent evidence suggests that increased oxygen delivered to the brain after cardiac arrest may be an important factor in preventing neuronal damage, resulting in an interest in hyperbaric oxygen (HBO) therapy. Interestingly, increased oxygen supply may be also reached by application of normobaric oxygen (NBO) or hyperbaric air (HBA). However, previous research also showed that the beneficial effect of hyperbaric treatment may not directly result from increased oxygen supply, leading to the conclusion that the mechanism of hyperbaric prevention of brain damage is not well understood. The aim of our study was to compare the effects of HBO, HBA and NBO treatment on gerbil brain condition after transient forebrain ischemia, serving as a model of cardiac arrest. Thereby, we investigated the effects of repetitive HBO, HBA and NBO treatment on hippocampal CA1 neuronal survival, brain temperature and gerbils behavior (the nest building), depending on the time of initiation of the therapy (1, 3 and 6 h after ischemia). HBO and HBA applied 1, 3 and 6 h after ischemia significantly increased neuronal survival and behavioral performance and abolished the ischemia-evoked brain temperature increase. ...The results show that HBO and HBA applied between 1 and 6 h after ischemia prevent ischemia-evoked neuronal damage, which may be due to the inhibition of brain temperature increase, as a result of the applied rise in ambient pressure, and just not due to the oxygen per se. This perspective is supported by the finding that NBO treatment was less effective than HBO or HBA therapy. The results presented in this paper may pave the way for future experimental studies dealing with pressure and temperature regulation. Malek, et al. (2013) in "Hyperbaric oxygen and hyperbaric air treatment result in comparable neuronal death reduction and improved behavioral outcome after transient forebrain ischemia in the gerbil"

Hyperbaric O2 therapy appears to have several protective mechanisms of action in severe TBI, likely increasing its potential effectiveness. These mechanisms have been demonstrated in both experimental and clinical investigations and include improved oxidative metabolism and mitochondrial function and reductions in intracranial hypertension, apoptosis, neuroinflammation, and free radical–mediated damage. The results of the present randomized clinical trial help to support these findings. Rockswold, et al. (2013) in "A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury"

Early or delayed multiple sessions of low atmospheric pressure HBOT can reduce intracranial pressure, improve mortality, as well as promote neurobehavioral recovery. The complimentary, synergistic actions of HBOT include improved tissue oxygenation and cellular metabolism, anti-apoptotic, and anti-inflammatory mechanisms. Thus HBOT may serve as a promising neuroprotective strategy that when combined with other therapeutic targets for TBI patients which could improve long-term outcomes. Huang & Obenaus (2011) in "Review: Hyperbaric oxygen therapy for traumatic brain injury"

HBOT is the only non-hormonal treatment approved by the FDA for the repair and regeneration of human tissue. Six of the 13 approved indications are directly related to brain injury and wound repair relevant to treating TBI. The USA Olympic team has now brought in HBOT to treat sports related injuries as part of their armamentarium.
The treatment of traumatic brain injury with hyperbaric oxygen is evolving rapidly. A plethora of cellular studies demonstrate the mechanisms of favorable action of HBOT and animal studies have also been able to add to the clinical rationale and utility for treating a variety of traumatic and ischemic brain injuries. Controlled randomized clinical trials have demonstrated efficacy of HBOT for traumatic brain injury. Therefore, the time has come for this orphan therapy to be adopted and for it to take its place as standard practice for treating both acute and chronic TBI. Stoller (2011) in "Hyperbaric oxygen therapy (1.5 ATA) in treating sports related TBI/CTE: two case reports"

In this study, 15 subjects who developed an attention deficit disorder (ADD) and slowing of reaction time at the time of exposure to mold toxins were identified. . . After ten sessions of hyperbaric oxygen treatment (HBOT), a statistically significant improvement was seen in both measures. This preliminary study suggests promising outcomes in treating mold-exposed patients with hyperbaric oxygen. Ezra, Dang, & Heuser (2010) in "Improvement of attention span and reaction time with hyperbaric oxygen treatment in patients with toxic injury due to mold exposure"

Cerebral Palsy

Danielle's Foundation, a non profit resource for families of children with Cerebral Palsy and brain injuries, provides valuble information and awards grants to assist families in need.

Visit MUMS National Parent-to-Parent Network to read testimonials from families who have tried HBOT for Cerebral Palsy.

CP is most often caused by an ischemic/hypoxic injury during the perinatal period. While hypoxia may cause cell death, there may sometimes be a zone called the "ischemic penumbra," in which brain cells receive just enough oxygen to survive, but not enough to function normally.
...With less severe hypoxia, some researchers believe that cells can survive for a long time in an "idling" state, and might be reactivated if blood flow is restored. Those who observed a decrease in spasticity and functional improvements with HBOT hypothesized that neurons might be viable but inactive much longer than previously believed.
Other mechanisms have also been suggested to explain the sometimes astonishing improvements described both by researchers and by the parents of children submitted to HBOT. Increased oxygenation is known to enhance neovascularization in wounds, burns, and other types of lesions; perhaps the same could occur in cerebral lesions. Additionally, increased oxygen might improve the metabolism and function of the remaining normal cells. It has been shown that lowpressure hyperbaric oxygen therapy(LPHBOT) can induce cerebrovascular changes and improve cognitive function in a rat traumatic brain injury (TBI) model.
...Many researchers have demonstrated, using cerebral single photon emission computerized tomography (SPECT scans), increased vascular activity in the brain following treatments in a hyperbaric chamber.
...The 10 studies on the treatment of CP with HBOT presented in Table 3, even though some have a small number of participants, have all demonstrated significant and often impressive improvements compared with what is seen from the majority of known and accepted therapeutic approaches for this condition. In fact, depending on the age and the severity of the condition of children with CP, the rate of progress (see Table 4) measured with the GMFM can be up to five times higher than the one obtained with intensive physiotherapy (PT) or even after rhizotomy followed by intensive PT. So far, no recognized approaches in the treatment of CP have shown faster or more impressive positive changes in gross motor function. Moreover, most recognized approaches like PT or rhizotomy do not improve cognition or communication. HBOT has an effect on global function of the brain and, besides the very important changes in motor function, the most common improvements reported by more than 80% of the parents are in cognition and language.Sénéchal, et al. (2007) in "Hyperbaric Oxygenation Therapy in the Treatment of Cerebral Palsy: A Review and Comparison to Currently Accepted Therapies"

Fibromyalgia

A supportive clinical observation for the notion that HBOT is indeed inducing neuroplasticity and is not merely "pain killer therapy" is the fact that a significant number of patients reported an increase or change in the pain sensation during the first 10-20 session. Consequent to this period of changed/increased pain sensation, patients reported a more comprehensive change beyond pain alleviation, including improvement in sleep characteristics and cognitive functions, more energy for daily tasks and improvement in general wellbeingEfrati, et al. (2015) in "Hyperbaric Oxygen Therapy Can Diminish Fibromyalgia Syndrome - Prospective Clinical Trial"

Inflammation

The purpose of this experiment was to explore the effect of hyperbaric oxygen treatment on carrageenan-induced inflammation and pain in rats. Hyperbaric oxygen treatment significantly decreased inflammation and pain following carrageenan injection. Clinically hyperbaric oxygen may be used in situations where NSAIDS are contraindicated or in persistent cases of inflammation.Wilson, Wilson, & Fuchs (2006) in "Hyperbaric oxygen treatment decreases inflammation and mechanical hypersensitivity in an animal model of inflammatory pain"

Pain

Recently, the beneficial effect of HBOT has been suggested in the treatment of pain disorders, including delayed onset muscle soreness,^15,16 fibromyalgia,¹⁷ inflammatory pain,¹⁸ and complex regional pain syndrome.¹⁹ The mechanisms underlying the beneficial effect of HBOT are unknown, but some beneficial effects of HBOT may be attributable to an altered inflammatory process. HBOT has been shown to enhance some aspects of host defense and its overall effect seems to be immunosuppressive.²⁰
. . . HBOT decreased inflammation and mechanical hypersensitivity in an animal model of acute inflammatory pain.¹⁸ HBOT may be comparable to acetylsalicylic acid treatment in alleviating joint inflammation and reducing mechanical hyperalgesia in an animal model of arthritis.³⁰ These studies show that HBOT produced a prolonged antinociceptive effect in animals that persisted after cessation of treatment. Thompson et al.²⁶ recently evaluated the effect of HBOT on 2 common models of neuropathic pain, L5 ligation and CCI of the sciatic nerve. In their study, HBOT was administered for 90 minutes at 2.4 ata after surgical manipulations daily for 2 weeks. They observed that both models demonstrated significant improvement in response to treatment over the course of the 2-week period, with CCI animals recovering more quickly and maintaining this recovery throughout the posttreatment period. They suggested that HBOT seems to be successful in relieving neuropathic pain for an extended period of time, and future research should be aimed at investigating the precise mechanisms underlying this positive effect. Our present study confirms their observations that HBOT reduced CCI-induced neuropathic pain, and further shows that the alleviated neuropathic pain was associated with significantly reduced TNF-α production in the affected sciatic nerve. Fenghua, et al. (2010) in "Hyperbaric Oxygenation Therapy Alleviates Chronic Constrictive Injury–Induced Neuropathic Pain and Reduces Tumor Necrosis Factor-Alpha Production"

Post Traumatic Stress Disorder & Post Concussive Syndrome

Forty 1.5 ATA HBOT sessions in 1 month was safe in a military cohort with chronic blast-induced PCS and PTSD. Significant improvements occurred in symptoms, abnormal physical exam findings, cognitive testing, and quality-of-life measurements, with concomitant significant improvements in SPECT. . . Sixty-four percent of the patients on psychoactive and narcotic prescription medications were able to decrease or eliminate use of these medications. Harch, et al. (2012) in "A Phase I Study of Low-Pressure Hyperbaric Oxygen Therapy for Blast-Induced Post-Concussion Syndrome and Post-Traumatic Stress Disorder"

Stroke

In this study we provide, for the first time, convincing results demonstrating that HBOT can induce significant neurological improvement in post stroke patients. The neurological improvements in a chronic late stage demonstrate that neuroplasticity can be operative and activated by HBOT even long after acute brain insult. Thus, the findings have important implications that can be of general relevance and interest in neurobiology. Although this study focused on stroke patients, the findings bear the promise that HBOT may serve as a valuable therapeutic practice in other neurological disorders exhibiting discrepancy between the anatomical and functional evaluation of the brain. Efrati, et al. (2013) in "Hyperbaric Oxygen Induces Late Neuroplasticity in Post Stroke Patients - Randomized, Prospective Trial"

Hyperbaric oxygen (HBO) has been used as a primary oradjunctive stroke therapy over years. Mechanism of the neuroprotection of HBO treatment after ischemia was thought to be mediated by improving oxygen supply [3]. A good body of evidence suggests that HBO treatment is neuroprotective. HBO treatment can decrease infarction volume on MRI examination and improve neurological outcome [4]. Hyperbaric oxygen was also found to decrease ischemia reperfusion injury induced by neutrophil [5]. Researchers have also demonstrated that exposure to HBO will cause rapid mobilization of bone marrow stem cells in humans,and the number of bone marrow stem cells (BMSCs) remains elevated in peripheral blood during the course of HBO treatments [6]. . .Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.Ying-Sheng Lee, et al. (2013) in "Long Course Hyperbaric Oxygen Stimulates Neurogenesis and Attenuates Inflammation after Ischemic Stroke"

The present study suggests that HBOT may be effective for acute ischemic stroke patients, and the efficacy of therapy is more obvious later in the disease course. A comparison of the two groups at one month revealed that the HBOT group had better outcome than the control group . . . Although the early efficacy of HBOT did not reach the statistic significance, it did reveal the tendency of better outcome compared to the control group. There are possible explanations. One, the mechanisms of HBOT for ischemic stroke (i.e., protection of the blood-brain barrier) repair and generate new blood vessels to the parts of the brain that have been injured, inhabited by apoptosis, and improve metabolism after ischemia [6]. All of these effects may take time to occur. Two, cerebral edema always develop soon after stroke onset and peak at about 24–96 hours. It decreases blood flow and influence oxygen delivery [21]. Three, since HBOT is an adjunctive treatment for ischemic stroke, patients during the acute stage of ischemic stroke, also received other treatments like antiplatelet therapy and/or cerebral circulatory agents, which are the mainstay treatment for ischemic stroke. Therefore, HBOT may not show its adjunctive effect significantly in mild stroke. Four, the patients included in this study are of mild severity. The degree of improvement for moderate-to-severe stroke may be more obvious than that of mild disease. Cheng-Hsin Chen, Shao-Yuan Chen, Vinchi Wang, et al. (2012) in "Effects of Repetitive Hyperbaric Oxygen Treatment in Patients with Acute Cerebral Infarction: A Pilot Study"

Wound Healing

RESULTS: In hyperbaric oxygen group, the healing time of 64 wounds was (16.7 +/- 1.8) d, while it was (20.2 +/- 2.3) d in the control group, suggesting a significant difference between two groups (P < 0.05). The incidence of hyperplastic scar was lower (38/64, 59. 4% ) in hyperbaric oxygen group than that (52/ 64, 81.2%) in control group with significant difference between them (P < 0.05).
. . . CONCLUSIONS: The hyperbaric oxygen can promote wound healing and effectively inhibit the early hyperplastic scar in rabbits ears. Zhang Q, et al. (2013) in "Effect of hyperbaric oxygen on the scar formation at the rabbit ears at an early stage"

Studies on the effects of HBO2 on inflammatory mediators may not only explain its mechanism of action, but also expand its clinical application. The main conclusion of this review is:

1. The angiogenic action of HBO2 may be a result of increased VEGF and NO production.
2. The immunosuppressive effect of HBO2 may be due to reduction of IL-1 production.
3. The anti-inflammatory effect of HBO2 may be due to inhibition of IFNγ, PGs, TNFα, IL-1, and IL-6.
4. The beneficial effect on ischemia-reperfusion injury may be due to up-regulation of bcl-2 and TGF and reduction of neutrophil 2–integrin.
5. HBO2 may stimulate local and general immunity because it decreases PGs, IL-1, and IL-10.
6. Vasoconstriction may be due to inhibition of NO and liberation of endothelin.
7. The anti-inflammatory effect of HBO2 may stimulate the use of HBO2 in acute or chronic inflammatory diseases in which large amounts of PGs are produced.
8. HBO2 raises PGE levels close to normal values in patients with duodenal ulcer. This may encourage the use of HBO2 in patients with duodenal or gastric ulcer.

Generally, the final conclusion regarding effects of HBO2 on various mediators of inflammation is not fully documented and waits further clinical and laboratory investigation. Absolutely, conclusive results could pave the way for new applications of HBO2.Al-Waili & Butler (2006) in "Effects of Hyperbaric Oxygen on Inflammatory Response to Wound and Trauma: Possible Mechanism of Action"

HBO improves tissue oxygen tensions by increasing plasma-based oxygenation and increasing erythrocyte deformability. Intermittent hyperoxia stimulates fibroblast and collagen synthesis, enabling angiogenesis, tissue repair and optimal healing. Hyperoxic vasoconstriction resolves oedema without impairing oxygen delivery, and reverses the ischaemia-oedema cycle. HBO also antagonizes free-radical-associated lipid peroxidation, reducing reperfusion injury.
Published research is limited, but a high quality randomized controlled trial in 1996 demonstrated significant improvement in healing with HBO. Cost benefits are substantial, by minimizing the many costly complications of ATPIs. Adjunctive HBO increases tissue oxygenation and decreases oedema, facilitating surgical repair and other treatments. Gill & Bell (2004) in "Review: Hyperbaric oxygen: its uses, mechanisms of action and outcomes"