**3. Traumatic brain injury basics**

*Advancement and New Understanding in Brain Injury*

ment. Over 7500 successes cannot be entirely wrong.

effective for this fourteenth indication, or disease state.

(resulting from rapid decompression and blast injury [6].)

discussed. The conclusion is simple: coverage of HBOT for TBI.

**2. Background**

cholera, and the plague, it infects more people than all the others combined. Yet conventional medicine already knew that ulcers were caused by stress. An entire set of industries grew up around "healing" stress and its aftermath: antacids, stomach surgery for bleeding ulcers, gastritis, stomach cancer, depression. "To gastroenterologists, the concept of a germ causing ulcers was like saying that the Earth is flat." [1] To them, the cause of all the illness and death was psychosomatic, "all in the head." Marshall went so far to prove his point that he gave himself ulcers by drinking a broth of H.pylori and curing himself. And still not recognition. Cut to the chase: For their relentless persistence and science on H.pylori, in **2005** Marshall and Warren won the Nobel Prize. Treatment with an antibiotic is standard medicine for stomach cancer [2]. Twenty-four years to go from goats to Nobel laureates. Along the way, the men were ridiculed and denounced by learned councils around the world. And then the "truth." As you read these pages, we expect that you will be whipsawed by the truths exposed as authors and readers wonder about the answer to the Obvious Question: *Since this works, why are they opposed to it?* As you will see, there are no complete answers, but the data and the peer-reviewed research do provide compelling and overwhelming evidence of the safety, efficacy, and cost-effectiveness of this treat-

On August 30, 2002, Medicare announced its intention to issue a national coverage determination (NCD) for Hyperbaric Oxygen Therapy (HBOT) in the treatment of diabetic wounds of the lower extremities. The arguments that led to that determination [3] established that oxygen under pressure was safe and

The evolution in thinking and the subsequent research was enabled by the 1999 refinement and restatement of the drug definition of HBOT as the use of greater than atmospheric pressure oxygen as a drug to treat basic pathophysiologic processes and their diseases [4]. The UHMS defines hyperbaric oxygen (HBO2) as an intervention in which an individual breathes near 100% oxygen intermittently while inside a hyperbaric chamber that is pressurized to greater than sea level pressure (1 atmosphere absolute, or ATA) [5]. With that definition the totality of on-label indications could be understood as cohesive sets of diagnoses connected by HBOT effects on the

acute and/or chronic underlying pathophysiology common to the diseases.

Doctors noticed that the definition necessarily could be applied to the use of HBOT for additional diseases that shared this pathology. Of the 14/15 indications accepted by the FDA/CMS, at least five are non-healing wounds and therefore closely related to brain wounding from blast, falls, impact, stroke, Improvised explosive devices, and concussion. Those indications are: Crush injury, compartment syndrome, and other acute traumatic ischemias; Arterial Insufficiency, entailing enhancement of healing in selected problem wounds (includes uses like Diabetic Foot Wounds, Hypoxic Wounds); Radiation tissue damage (soft tissue and bony necrosis); Skin grafts and flaps (compromised); and Air or gas embolism

The accurate drug definition of HBOT, and its implications for the findings and data in research into traumatic brain injury, is used in this paper to argue for HBOT safety and effectiveness in the treatment of Traumatic Brain Injury. The argument is constructed by identifying the underlying pathophysiology in traumatic brain injury. Evidence for the beneficial effects of HBOT on TBI is presented. Benefits to patients with TBI is discussed. Evidence for HBOT for TBI risk/benefit and cost/are

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Research over the last two decades has revealed the complex microcosms of multiple pathophysiological processes resulting from insults to the brain, including traumatic brain injury [7]. The three essential components determining the outcome of head injuries are brain blood flow; the pressure in the skull leading to swelling; and hypoxia, the lack of oxygen [8].

According to the Centers for Disease Control and Prevention (CDC), "traumatic brain injury (TBI) is caused by a bump, blow or jolt to the head or a penetrating head injury that disrupts the normal function of the brain." TBI severity ranges from "mild," i.e., a brief change in mental status or consciousness to "severe," i.e., an extended period of unconsciousness or amnesia after the injury [9]. The CDC keeps current statistics on TBI death and disability.

Traumatic brain injury (TBI) is a major cause of death and disability in the United States. Those who survive a TBI can face effects that last a few days, or the rest of their lives. Among TBI-related ED visits and hospitalizations in 2014, statistics notable for the CDC include:


UCLA researchers, citing animal and human studies, speak of "a neurometabolic cascade of events that involves bioenergetic challenges, cytoskeletal and axonal alterations, impairments in neurotransmission and vulnerability to delayed cell death and chronic dysfunction.. .. linking the neurometabolic cascade to clinical characteristics as well as on new connections being made between acute postconcussion pathophysiology, long-term biological changes and chronic sequelae." [14] Further: "The etiology of postconcussive syndrome is debated, but may be caused by diffuse axonal injury or persistent metabolic alterations resulting in neuronal dysfunction and develops in 38–80% of patients with TBI…." [15].

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 the wounding from the brain injury.

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.

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

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 and the body will suffer in time.

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*Hyperbaric Oxygenation in the Treatment of Traumatic Brain Injury*

**4. Hyperbaric oxygenation mechanisms of action**

many effects, HBOT has been shown to be effective in:

• Reducing local swelling (edema) and reperfusion injury

• Releasing nitric oxide with migration to point of injury

• Releasing stem cells with migration to area of injury

• Improving blood flow to the affected area of the brain

• Generating blood vessel growth (angiogenesis)

• Restarting stunned cellular metabolism and stunned mitochondria

• Decreasing markers of inflammation in the body and brain [23]

• Activating stem cells 8x normal to repair neural pathways (neurogenesis)

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].

Several studies have looked at this downward cycle in untreated brain injuries

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

• Improving and repairing injury, by increasing oxygen delivery to damaged

[22] and noted a correspondence between the symptoms resulting from that brain injury and the HBOT Mechanisms of Action that work to arrest and heal the

*DOI: http://dx.doi.org/10.5772/intechopen.94401*

traumatic brain injury.

• Promoting wound healing

• Improving infection control

• Increasing the production of collagen

tissues

*Hyperbaric Oxygenation in the Treatment of Traumatic Brain Injury DOI: http://dx.doi.org/10.5772/intechopen.94401*

Several studies have looked at this downward cycle in untreated brain injuries [22] and noted a correspondence between the symptoms resulting from that brain injury and the HBOT Mechanisms of Action that work to arrest and heal the traumatic brain injury.
