Hyperbaric Oxygen Therapy (HBOT) is described as breathing increased amounts of oxygen within a pressurized environment, at a level higher than the average atmospheric pressure exerted at sea level (1 Atmosphere Absolute, ATA). When this occurs, a variety of physiological changes occur within our body that support healing. HBOT promotes improvement of oxygen delivery to all cells and tissues in our body, decreases acute and chronic inflammation, formation of new blood vessels, turns on healthy genes and turns off unhealthy genes - epigenetics, reverses hypoxia (low oxygen), increases microcirculation, enhances Cerebrospinal Fluid (CSF) and lymphatic flow, stimulates stem cell release, promotes balance of autonomic nervous system function and optimizing all stages of wound healing. This novel treatment has potential to revolutionize healthcare related to Traumatic Brain Injury.
Henry’s Law states that increasing pressure levels will increase the amount of dissolved gas available in a fluid. In our body, that translates to oxygen diffusion into the plasma of our blood. Oxygen levels rise anywhere from 46-1200%, varying by level of pressure and oxygen concentration. Under normal conditions, the delivery of oxygen to our cells and tissues is primarily through Red Blood Cells (RBCs) that travel within our circulating blood. There are 250,000,000 hemoglobin molecules on an individual RBC, and each RBC can carry 1 billion oxygen molecules (4 on each hemoglobin binding site). This is known as oxygen carrying capacity. Most of these sites are already oxygen bound in people with normal lungs (97-100% is common) at sea level. If a Functional Neurologist has used a pulse oximetry meter on you at any time, they are measuring the percentage of sites available on hemoglobin to bind oxygen, as well as measuring your arterial oxygen saturation. Under increased pressure during HBOT, oxygen is not only attached to hemoglobin molecules on the RBC’s, but also is directly dissolved into the plasma (liquid) of the blood. This is the key to the power of HBOT - it allows for supra-physiologic levels of oxygen to be diffused into the body through the plasma of our blood due to Henry’s Law of Gases - Physics 101! At a pressure that is three times sea level, or 3 Atmosphere Absolute (ATA), you no longer require Red Blood Cells to carry oxygen. Enough oxygen is dissolved in the plasma at this pressure that the human body is able to maintain all physiological functions without RBC’s. This is the reason that HBOT is used at higher pressure for acute trauma and severe anemia (12). This combination of oxygen and pressure is critical to achieving a biological response, even with pressures that are thought to be trivial or non effective (3). Pressure is critical…without pressure such physiological changes are not possible.
Pressure increases all fluid dynamics, increasing Cerebral Spinal Fluid (CSF) and lymphatic flow, as well as forcing blood further into our tissues and delivering oxygen deeper into our brains. This phenomena would not be possible under normal conditions. Our CSF bathes our brain and spinal cord, delivering important nutrients and materials, while also removing toxins and waste that occurs as a result of normal metabolic activity. The atmospheric pressure that changes through HBOT help stimulate blood and lymphatic flow, improving detoxification mechanisms and delivery of important nutrients. When healing, cells and tissues produce a lot of cellular waste that needs to be cleaned up. HBOT facilitates this. This increase in oxygen delivery to our brain is extremely important for allowing our cells to create energy and heal themselves. This treatment would help counter-act the diffuse damage to the brain after a concussion (1).
This increase in blood flow improves microcirculation within our bloodstream. The more oxygen content we have dissolved within the fluid, or plasma of our blood, the deeper oxygen penetrates into our surrounding tissues. This is a result of the diffusion gradient that higher blood levels of oxygen is able to produce. The increased oxygen delivery that occurs deep within our cells and tissues, allows us to create tremendous amounts of energy. Specifically, it produces Adenosine Triphosphate (ATP), which is the energy required for regeneration, repair and healthy function of all cells within the human body. Without ATP, we cannot maintain any process in the human body and mind, and our cells will weaken and may die.
The acute effects of HBOT are an immediate decrease in inflammation, swelling and pain. Due to down regulating inflammatory pathways and constricting blood vessels that allow less leakage of fluid from an injured vessel. Despite this constriction (which is mild), the net is an increase in the amount of oxygen delivered to the tissue because of the supersaturation in the plasma. In an acute trauma, constricting blood vessels will prevent leakage from injured vessels, thus decreasing swelling and inflammation in the surrounding tissue. If, for example, one of these damaged blood vessels is in your brain, decreasing that swelling can save your life. A few years ago, there was a phase II study on patients who had suffered severe traumatic brain injuries. They received just three HBOT sessions within the first 72 hours of concussion presentation. The authors showed that HBOT acutely decreased intracranial pressure and, as a result, significantly decreased mortality. They also found a decrease in morbidity/disability over the long term as well. A phase III study is underway now (11-13). HBOT reverses hypoxia (low oxygen levels) in tissue by diffusing oxygen much farther into said tissue (approximately 4x at 2 ATA) and, by way of the diffusion gradient that was described earlier, can potentially oxygenate tissue that is at risk of dying from an acute injury (trauma).
The long-term effects of HBOT occur from frequent treatments over a directed amount of time. HBOT increases production of crucial cells that our brain uses to heal itself after a concussion, called stem cells. Once produced, these stem cells can then travel to specific areas of injury or inflammation and turn into any type of tissue that’s needed to accelerate healing. There continues to be an increase in stem cell release past the 40th consecutive HBOT treatment as these stem cells mature to make new bone, new cartilage, new brain tissue, etc. The University of Pennsylvania School of Medicine found that stem cells were increased eight-fold with HBOT treatments due to its ability to increase synthesis of a molecule called nitric oxide, in the bone marrow, which is thought to trigger stem cell production (2). HBOT also modulates at least 8,000 genes via Reactive Oxygen Species (ROS), suppressing genes that are responsible for inflammation and apoptosis (programmed cell death), while also facilitating the expression of genes that are responsible for growth, repair, and decreasing inflammation. This epigenetic shift actually starts happening immediately with your first treatment, but continuous and frequent HBOT exposure amplifies and solidifies these catalytic shifts (12,13). It’s like a great scaffold rebuilder, with longer protocols where you can grow new blood vessels, connective tissues, bone, cartilage, neurons, and supporting cells in the brain. HBOT works to rebuild our cytoarchitecture! It also down-regulates inflammatory cytokines (IL 1, 6, 8, 12, TNF alpha), help rid your body of senescent cells (also known as “zombie cells” because they no longer divide and are associated with aging, cancer and inflammation) and more. Recent studies also show that it can regenerate blood vessels in the brain, around the heart and even in our sexual organs (12, 13). This can sustain a tissue’s health and provide the nutrients it needs over the long term. Another study was released from Israel that found hyperbaric treatments may contribute to age reversal. They determined that 60 treatments at 2.0 ATA pressure over 3 months increased telomere (chromosomal protection to help cellular function) length by 20% and decreased senescent cell populations by 37% (14).
HBOT is believed to improve and regulate Autonomic Nervous System (ANS) function. One of the main jobs of the ANS is to deliver blood flow when and where we need it. When we use our brain for any activity, we need to give it fuel, or oxygen to complete its task. If you’ve ever stood up too quickly and have been light headed or dizzy, you’ve most likely experienced autonomic dysregulation. HBOT is theorized to have two major affects on the ANS, one a direct affect to the pressure regulatory systems and another to healing the regions of the brain stem and cortex that are directly involved in the control of the ANS and often injured after a traumatic brain injury.
After a concussion, acute effects occur that start impacting our brain immediately. Because of this, we undergo a neurometabolic cascade. During this time, inflammation is occurring within our injured brain and an “energy crisis” is occurring due to limited blood flow that cannot provide adequate amounts of glucose and oxygen to our brain. This fuel is what we require for cellular repair and function. Once we use up all of our glucose, our brain goes into a “depressed metabolism” state where levels of calcium can spike and further worsen our energy crisis and lead to cellular death. In addition, calcium levels are linked to inflammation, decreased magnesium, altered neurotransmission and increased free radical production (15). I hope by now you’re starting to think, “An energy crisis? Reduced blood flow? Inflammation spiking? I know a way that may help mitigate this - Hyperbaric Oxygen Therapy!! The use of Hyperbaric Oxygen Therapy not only decreases inflammation while providing increased oxygen to produce energy, we might infer that it could deliver more glucose through circulation to give fuel to our injured brain as blood and cerebrospinal fluid (CSF) flow are increased. In addition, the removal of waste buildup that would accumulate during this metabolic event would be through an increase in lymphatic and CSF flow. All the while we are reversing hypoxia and providing energy to improve neural connectivity that is disrupted during head trauma.
As a result of delivering more oxygen to the brain, HBOT provides a framework in which healing can be accelerated after a TBI. Within this framework, it must also be noted that injured neurons also benefit from being stimulated at the appropriate metabolic rate. Specific areas of our brains have specific functions and therefore respond to certain stimuli. We can target these areas, and when the brain is provided with the appropriate stimuli for its region, it starts to grow. Its neurons branch out to promote connectivity with its neighboring neurons and is sometimes called synaptic arborization. This process of creating and reorganizing neural connections between brain cells in response to learning or after injury, is known as Neuroplasticity. It’s how we undergo any change in thought or habit in our mind. These new connections allow us to communicate and send messages to other areas of our brain, as well as to the body which helps increase speed and processing capability, balance, coordination, modulate pain, improve eye movements, regulate emotions and restore overall function that may be experienced after TBI. As a Functional Neurologist, that’s my job; but without adequate energy, this process is lengthy and sometimes difficult. Therefore, we consider incorporating HBOT to improve oxygen delivery to the brain that will create added energy required during healing and growth. As such you will have the opportunity to create a more robust neuroplasticity response.
The Journal of Neurology agrees and states that there is B-level research for the use of HBOT as viable treatment of PPCS/TBI symptoms and can alleviate post traumatic stress disorder symptoms secondary to a brain injury in 5 out of 5 peer-reviewed clinical trials. The clinical improvements seen in the participants are large and consistent through each of the studies. Studies suggest that lower pressures (<2.0 ATA) and lower oxygen levels (<100% O2) are potentially better for mTBI/PPCS and PTSD symptom recovery. The heterogeneous nature of a TBI should not bias the physician from overlooking the ability of HBOT (or HBAT) in assisting or accelerating repair of the brain (3). This is a profound result for concussion patients as earlier intervention could reduce the potential for Persistent Post Concussion Syndrome (PPCS), that can occur with 25% (1) or more of concussions. Not only are there promising results for patients with PCS, but there is evidence and support as to why we would apply this treatment immediately after a patient experiences a TBI. My contention is that HBOT should be applied at all states of concussion healing and treatment.
Oxygen is life-giving. It is required for us to heal and necessary for every bodily function. The pressure from Hyperbaric is critical and it is what stimulates all of the mechanisms described in this chapter. The application of HBOT is simple, effective and affordable as mild chambers have been shown to be most effective for neurocognitive conditions such as TBI. If you have suffered from TBI
It should be noted that there are 14 FDA approved conditions for HBOT in the US, whereas there are over 70 approved conditions in China, Japan and Russia. That being said, TBI treatment is still categorized as investigational, despite the significant amount of research that is supporting it (12).
Boussi-Gross R, Golan H, Fishlev G, Bechor Y, Volkov O, Bergan J, Friedman M, Hoofien D, Shlamkovitch N, Ben-Jacob E, Efrati S. Hyperbaric oxygen therapy can improve post concussion syndrome years after mild traumatic brain injury - randomized prospective trial. PLoS One. 2013 Nov 15;8(11):e79995. doi: 10.1371/journal.pone.0079995. PMID: 24260334; PMCID: PMC3829860.
(2) University of Pennsylvania School of Medicine. "Penn Study Finds Hyperbaric Oxygen Treatments Mobilize Stem Cells." ScienceDaily. ScienceDaily, 28 December 2005. <www.sciencedaily.com/releases/2005
(4) Miller RS, Weaver LK, Bahraini N, Churchill S, Price RC, Skiba V, Caviness J, Mooney S, Hetzell B, Liu J, Deru K, Ricciardi R, Fracisco S, Close NC, Surrett GW, Bartos C, Ryan M, Brenner LA; HOPPS Trial Team. Effects of hyperbaric oxygen on symptoms and quality of life among service members with persistent postconcussion symptoms: a randomized clinical trial. JAMA Intern Med. 2015 Jan;175(1):43-52. doi: 10.1001/jamainternmed.2014.5479. PMID: 25401463.
(5) Harch PG, Andrews SR, Fogarty EF, Amen D, Pezzullo JC, Lucarini J, Aubrey C, Taylor DV, Staab PK, Van Meter KW. A phase I study of low-pressure hyperbaric oxygen therapy for blast-induced post-concussion syndrome and post-traumatic stress disorder. J Neurotrauma. 2012 Jan 1;29(1):168-85. doi: 10.1089/neu.2011.1895. Epub 2011 Nov 22. PMID: 22026588.
(6) Harmon, K. G. et al. 2013. American Medical Society for Sports Medicine position statement: concussion in sport. British Journal of Medicine. 47(1), 15-26.
(7) McCrory, P. et al. 2013. Consensus statement on concussion in sport: the 4th international conference on concussion in sport, Zurich, November 2012. Journal of Athletic Training, 48(4), 554-575
(9) Lazzarino, G. et al. 2012. The importance of restriction from physical activity in the metaoblic recovery of concussed brain. Brain Injury: Pathogenesis, Monitoring, Recovery, and Management. Reijika, Croatia: Intech, 501-522.
(10) Asken, B. M. et al. 2016b "Playing it through" : Delayed reporting and removal from athletic activity after concussion predicts prolonged recovery. Journal of Athletic Training. 51(4), 329-335.
(11) Rockswold SB, Rockswold GL, Zaun DA, Liu J. 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. J Neurosurg. 2013 Jun;118(6):1317-28
(14) Hachmo Y, Hadanny A, Abu Hamed R, Daniel-Kotovsky M, Catalogna M, Fishlev G, Lang E, Polak N, Doenyas K, Friedman M, Zemel Y, Bechor Y, Efrati S. Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial. Aging (Albany NY). 2020; 12:22445-22456.
(15) Giza CC, Hovda DA. The Neurometabolic Cascade of Concussion. J Athl Train. 2001; 36(3): 228-235
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