**4. Hyperbaric oxygenation mechanisms of action**

Medical studies have shown that Hyperbaric Oxygen Therapy is medicine's best way to provide oxygen to all parts of the body in the shortest period of time. Among many effects, HBOT has been shown to be effective in:


*Advancement and New Understanding in Brain Injury*

the wounding from the brain injury.

Advanced neuroimaging reveals the basic neurobiology of concussion/mild TBI in animal models, which is increasingly corroborated in human studies. These images of the brain with such techniques as diffusion tensor imaging (DTI) validate

Since HBOT has been studied as a science for over 84 years [16], a wealth of evidence exists - with or without brain imaging or functional imaging such as SPECT scans - that points to the wounding of the brain as an underlying cause of TBI and, in many cases, the cooccurrence of Post-traumatic stress disorder (PTSD). Controversy continues to wage over proper diagnoses of TBI and PTSD. The author is aware for over a decade of clinical medicine and the accumulation of "anecdotal evidence" in over 7500 successful uses of HBOT to help treat and heal TBI, that those combat veterans presenting with "PTSD only" diagnoses from the VA are overwhelmingly afflicted with undiagnosed TBI. Researchers have not yet fully understood how TBI commonly affects the neurological and clinical presentation of PTSD [17]. Despite this high prevalence, the pathogenesis of TBI, PTSD and TBI/ PTSD remains largely unknown, hindering prevention and treatment efforts [18]. No matter how acquired, TBI in a veteran or a civilian, is an injury to the brain tissue. Damage is physiological, behavioral, and emotional. Symptoms can include altered consciousness; headaches; structural damage to brain matter and blood vessels and nerves; loss of neurological function that can lead to loss of motor, sensory, coordination, balance, vision, hearing and other abilities; inability to multi-task, slowed reaction time, decreased attention and concentration, inability to think fast; and frequent incapacity to work, sleep, relax, think or discern what is normal. When wounded, the brain, like all body organs, responds with the inflammatory process which proceeds to form scars, scar tissue, and chronic wounds. When the brain injury is compounded by post traumatic stress disorder (PTSD) the victim is subjected to hyperarousal, avoidance behaviors, trauma re-experiencing, increased mental vigilance, difficulty falling asleep, nightmares, constant anxiety resulting from progressive sleep deprivation and elevation of injurious stress hormones. Behaviors and emotions are magnified, intensifying the patient's negative responses: relationship problems, domestic violence, substance abuse, depression, criminal activity, unemployment, incarceration, homelessness, and too frequently suicide. Where the degenerative cycle can be arrested with drugs or psychological interventions, the result may be a lifetime of degraded quality of life on welfare –

not only for the patient but typically for the caregiver as well.

the accompanying effects, many of which are diagnosed as "only PTSD."

In 2016, researchers at the Uniformed Services University of the Health Sciences in Bethesda, Md., found evidence of tissue damage caused by blasts alone, not by concussions or other injuries [19]. According to the New York Times, this could be the medical explanation for shell shock and the sequalae of psychological problems called PTSD [20]. The implications are clear: IEDs, breeching, enemy and/or friendly fire from personal weapons can lead directly to physical brain damage and

Not to be overlooked are the complex interactions among brain injury, trauma, and physical/emotional/behavior/mental health. Psychiatrist Bessel van der Kolk, in The *Body Keeps the Score* [21], explains how trauma and its resulting stress harms us through physiological changes to body and brain, and that those harms can persist throughout life. Stress, trauma, depression, mental and physical health are so intertwined that it is hard to know the seat of the disease. The author argues that trauma is one of the West's most urgent public health issues. The list of its effects is long: on mental and physical health, employment, education, crime, relationships, domestic or family abuse, alcoholism, drug addiction. As with PTSD and TBI, whether a brain insult precedes mental health problems, it is certain that the brain

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and the body will suffer in time.


While it is uncommon to hear HBOT talked about in terms of healing wounds to the brain, the facts are now obvious: a major organ of the body is damaged. "Treatments" in the DoD and Veterans Administration for a brain-wounded population of at least 414,000 post-9/11 veterans typically resolve to rest and "a mix of cognitive, physical, speech, and occupational therapy, along with medication to control specific symptoms such as headaches or anxiety." [24] Virtually the last time TBI is referred to as a wound is when speaking of "the Invisible Wounds of War."

Brain wound healing demands that the body grow new tissue: blood vessels, connective tissue, new brain tissue. Cells have to grow and divide to form new tissue, necessitating stimulation of cells to divide and multiply. DNA must be stimulated [25]. By 2008 DNA analysts found that a single hyperbaric treatment turns on as many as 8101 genes in the 24 hours following HBOT treatment [26]. In short, "the turned-on genes are those genes that code for growth and repair hormones and the anti-inflammatory genes." [27] As already noted, HBOT is already approved for several on-label indications collectively similar as wound healing. It is worth noting that HBOT chambers are present in 1158 of a total of 3342 hospitals in the US [28].

Those chambers are primarily used for Wound Healing. For a variety of reasons, those chambers are not put to use on off-label uses of HBOT. Nevertheless, the bulk of science on animal and human patients with TBI has been collected in both hospital-based and private clinics.

Dr. Paul Harch prepared voluminous evidence on HBOT for wound healing in his arguments for recognition of DFW in 2002 [29]. More specific to TBI, Dr. Philip James, in "Head Injuries – the Curse of Life in the Fast Lane," [30] traces the development of HBOT-for-TBI research as far back as 1972 [31]. The study found that tissue oxygen levels that fight hypoxia rise with the increase in either the oxygen concentration or pressure: hyperbaric oxygenation. James writes that "*this one study* answers all the questions and objections raised about using hyperbaric oxygen treatment for patients with head injury." [32] Oddo in 2011 identified hypoxia as a culprit. Brain hypoxia is associated with poor short-term outcome after severe traumatic brain injury independently of elevated ICP, low CPP, and injury severity. Reduced brain oxygen (Pbto [2]) may be an important therapeutic target after severe traumatic brain injury [33]. Dr. Daphne Denham, the nation's premier expert on HBOT treatment of acute concussion, reported that 98% of her patients in her Fargo ND clinic [348 out of 350] treated within ten days of suffering a concussion, completely resolved their symptoms in five treatments or less [average of 2.4 treatments] [34]. The only difference in her patients and the thousands of concussed athletes in North Dakota who linger with symptoms for weeks and months using standard of care medicine [AKA "the tincture of time"] was HBOT. [NOTE: Maroon and Bost in 2011 write that nonpharmaceutical alternatives, dietary supplements and hyperbaric oxygen "may be a better first-line choice for the treatment of PCS, which has generally been underreported by both athletes and the military." [35] Of note for the CMS population is the work of Dr. Anne McKee on the connections between concussion and Chronic Traumatic Encephalopathy (CTE) [36]. "CTE is a progressive neurodegeneration clinically associated with memory disturbances, behavioral and personality change, Parkinsonism, and speech and gait abnormalities.... traumatic injury may interact additively with [Alzheimer's Disease] to produce a mixed pathology with greater clinical impact or synergistically by promoting pathological cascades that result in either AD or CTE."

Of no small importance is groundbreaking research from Washington State University. Researchers found that HBOT can halve the pain and symptoms of opiate withdrawal/detox [37].

And in current investigations of the use of HBOT to arrest and reverse the effects of COVID-19, preliminary evidence from China [38] (five cases) strongly suggests that based on the immutable science of HBOT and recent clinical application to deteriorating severely hypoxemic COVID-19 pneumonia patients, HBOT has significant potential to impact the COVID-19 pandemic. Fifty-eight patients as of this writing have been positively affected. Further, clinicians in at least five independent studies in the US using HBOT are raising the PO2 levels in patients in ICUs to the point where they avoid being put on ventilators and, in many cases, are being sent home after as few as five treatments [39].
