Plasticity is used in brain science to describe the brain's ability to change and adapt throughout an individual's lifetime in response to various environmental, cognitive, and developmental factors. This phenomenon is fundamental for the development of new skills, the formation of memories, and the recovery from injuries or diseases that affect brain function. Brain plasticity is based on the ability of neurons to modify their relationship, or connections, with other neurons in response to changes in neural activity. This process, known as synaptic plasticity, allows the brain to reorganize its networks and optimize its function in response to different events and challenges.
One of the most important forms of synaptic plasticity is long-term potentiation (LTP), which occurs when a synapse's repeated activation or stress strengthens the synaptic transmission, or connection, between the pre-and post-synaptic neurons. This process, the cellular basis of learning and memory, allows the brain to continuously remodel, adapt, and change how it interacts with the environment.
Another form of plasticity is neurogenesis, which refers to generating new neurons in the brain. This process is thought to occur primarily in two regions of the brain: the hippocampus, which is involved in learning and memory, and the olfactory bulb, which is involved in the sense of smell. Neurogenesis is thought to play a role in the adaptation of the brain to new experiences and the repair of brain damage.
The importance of plasticity lies in its implications for human health, well-being, and disease. Plasticity allows individuals to learn new skills, adapt to changing environments, and recover from injuries or diseases that affect brain function. For example, brain injury patients can benefit from neuroplasticity-based rehabilitation programs that help them relearn lost motor skills and improve their cognitive function.
Sensory experiences are the most important factors in creating plasticity. When an individual is exposed to multiple new sensory experiences or a singular impactful or stressful experience, the brain modifies its neural networks to optimize its functioning in response to these demands. This is known as experience-dependent plasticity, and it occurs throughout the lifespan. For example, learning a new skill, a first kiss, or a tragedy can lead to changes in the brain that facilitate remembering and repeating these experiences.
Another factor that contributes to plasticity is injury or neurological disease. When the brain is damaged by injury or disease, it can respond by reorganizing its neural networks to compensate for the damage. This is thought to be one of the primary mechanisms by which concussions may sometimes resolve on their own. This type of plasticity is known as "compensatory plasticity." It is the target and basis of many rehabilitation programs that aim to improve brain function after injury or disease. This is why concussion patients may benefit from rehabilitation programs that help them relearn sensory-motor processing skills by promoting compensatory plasticity.
Genetics also plays a role in brain plasticity. Some individuals may have a genetic predisposition to greater plasticity, allowing them to learn new skills more easily or recover quickly from brain injuries or diseases. Additionally, certain genes are involved in the regulation of synaptic plasticity and neurogenesis, which are two key mechanisms of plasticity in the brain regulating synaptic plasticity and neurogenesis,
Finally, several neurotransmitters and signaling molecules play important roles in neuroplasticity, which refers to the brain's ability to change and adapt in response to experience.
Some of the major neurotransmitters involved in neuroplasticity include:
In addition to neurotransmitters, several other types of signaling molecules play important roles in neuroplasticity, which refers to the brain's ability to change and adapt in response to experience. Some of the major signaling molecules involved in neuroplasticity include:
Overall, these signaling molecules work together to modulate plasticity in the brain. Their effects depend on the specific brain regions and circuits involved, as well as the timing and intensity of their release.
While brain plasticity is generally considered a positive trait that allows the brain to change and adapt throughout an individual's lifetime, not all forms of plasticity are good. In some cases, plasticity can be maladaptive and contribute to the development or persistence of neurological and psychiatric disorders.
One example of maladaptive plasticity, or plastic deformation, is the overgrowth of neural networks that occurs in some forms of epilepsy. In these cases, excessive synaptic connections can lead to seizures and other disorder symptoms. Similarly, plasticity can sensitize neural pathways in chronic pain conditions, increasing pain sensitivity and decreasing pain tolerance. Plasticity can lead to the sensitization of neural pathways in chronic pain conditions.
Other examples of maladaptive plasticity are the reorganization of neural networks that occurs in concussions, long-standing vestibular disorders, and even long-duration space flight where the brain has maladapted to micro-gravity and hypo-magnetism. While compensatory plasticity can help individuals regain lost function after these injuries, in some cases, maladaptive plasticity can lead to changes in neural connectivity that contribute to persistent sensory, cognitive, or motor deficits. Maladaptive plasticity can alter the way that an individual perceives themselves, the world that they exist, the way they think, their personality, and even subconscious functions (like their blood pressure, heart rate/rhythm, hormones, etc)
In addition, plasticity can be influenced by environmental factors or harmful or stressful experiences, such as exposure to chronic stress, trauma, or substance abuse. These experiences can lead to maladaptive changes in neural networks that contribute to developing mood and anxiety disorders, addiction, and other mental health conditions. For example, in post-traumatic stress disorder (PTSD), the reactivation and consolidation of traumatic memories can contribute to the persistence of the disorder.
Similarly, plasticity can also lead to strong associations between drug use and environmental cues, making it difficult to break the cycle of addiction.
Harnessing plasticity, or the brain's ability to change and adapt, can be a powerful tool for improving health and performance. By understanding plasticity mechanisms, researchers and clinicians can develop interventions promoting adaptive brain changes.
One way to harness plasticity for health and performance is through targeted training programs. Most training programs have a common, fundamental framework involving sensory-motor integration. If you think of the brain as a computer system, like a computer, it needs input to function (like a mouse or keyboard). The inputs for the brain are senses (olfaction, vision, audition, gustation, proprioception, and the one that everyone overlooks— vestibuloception). Each sense is fundamentally linked with a motor function to approach a stimulus or withdrawal from it. This is the basis of sensory-motor training. Once a person is introduced to a sensory stimulus and responds with a motor function, they sense their response and refine it to be either more efficient or more appropriate. This is called coordination and cognition. This is how athletes can benefit from training programs that employ sensory-motor drills to target specific neural networks involved in their sport, such as motor coordination or spatial awareness.
If sensory information is erroneous, the brain's sensory encoding is inaccurate and will create an inappropriate motor function. Think about this as "poor quality in yields poor quality out." Since sensory information is the foundation of motor function and cognition, correcting aberrancies in sensory processing is fundamental for most rehabilitation programs.
Another way to harness plasticity is through the use of device-generated brain stimulation techniques. Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are two of many non-invasive techniques that can modulate neural activity and promote plasticity in different brain regions. TMS can be used to stimulate specific regions of the brain, while tDCS can be used to enhance or suppress neural activity in targeted networks.
In addition, plasticity can be harnessed for all nervous system areas, including neurological and psychiatric disorders. For example, stroke patients can benefit from rehabilitation programs that promote compensatory plasticity to help them regain lost motor skills. Similarly, individuals with depression can benefit from cognitive-behavioral therapy, which promotes adaptive changes in neural networks involved in emotion regulation.
Furthermore, plasticity can also be harnessed for cognitive enhancement. For example, brain training games and other cognitive training programs can promote plasticity in the prefrontal cortex, which is involved in executive function and working memory. Additionally, mindfulness meditation has been shown to promote plasticity in the hippocampus, which is involved in learning and memory.
Jeffrey Kleim, Ph.D., a neuroscientist and expert on neural plasticity, has proposed 10 principles for applying the concept of plasticity to improve brain function. These principles guide designing interventions that promote neuron-to-neuron communication and adaptive changes in the brain.
Applying the ten principles of plasticity proposed by Jeffrey Kleim can guide the development of interventions that promote adaptive changes in the brain. These principles highlight the importance of specific and challenging training programs, the timing and intensity of interventions, and the emotional salience of tasks. Understanding plasticity mechanisms and designing interventions that harness their power can improve brain function and promote lifelong learning and growth.
Dr. Antonucci has spent the past decade learning and developing different ways to harness these ten principles of plasticity to help individuals with persisting concussion symptoms. The result is his immersive treatment program, which has helped thousands of patients live their best lives.
A great deal of thought has gone into creating our "Immersive Program," which is a 5-day program "inpatient-like" program. For this program, people travel to my facility, stay in a nearby hotel or house, and dedicate 100% of their week to making transformational changes in brain function and disconnecting from the stressors of home, work, school, and the rest of life ("Salience Matters"). This style of care also helps us manage the "Interference Matters" principle. Over these five days, I will construct a customized rehabilitation program based on an extensive evaluation. In a 3-hour evaluation, I comprehensively measure an individual's sensory-cognitive-motor system to identify any maladaptive plasticity using established and novel evaluation procedures. Once we have identified functions that need modification, I create an intervention program that specifically targets the tasks and networks that need to change ("Specificity Matters"). This involves doing something ("Use and Improve It") and NOT doing something ("Use it or Lose it") to reshape the targeted neurological networks. Patients are treated for two to three 60 to 90-minute, multi-modal daily sessions involving proprioception, vision/oculomotor, vestibular, coordination, and cognitive therapies, harnessing the "Transference Matters" principle. This schedule also allows us to build on the "Intensity Matters" and "Repetition Matters" principles.
Some principles or variables, such as age and timing, are more difficult to control and manipulate in a treatment program. We would love to see patients early in their injury and/or when they are young, but that isn't always possible. Despite not all of our patients being young or having "fresh" injuries, we have been fortunate to create life-changing transformations for most of them. Our results have been published in over 60 peer-reviewed medical publications, many of which can be found here: Dr. Antonucci's Publications on Loop: The Open Science Research Network
Molecular hydrogen (“H2”) is gaining recognition as a powerful therapeutic gas with numerous potential health benefits. Many are calling molecular hydrogen the universe’s “fountain of youth.” Hopefully, this article will explain why some people think that.
Hydrogen (H2) is the universe's lightest, smallest, and most abundant element. It can penetrate biomembranes and diffuse into the cytosol, making it highly effective at distributing itself throughout the body. H2 also can rapidly reach the nucleus and mitochondria, protecting nuclear DNA and mitochondria from damage (Ohsawa et al., 2007). Unlike most antioxidant compounds, H2 can easily pass through the blood-brain barrier.
In an earlier article, Dr. Antonucci discusses some of the benefits of molecular hydrogen in the context of concussion, but these benefits also exist in all individuals. In this article, we will review the mechanisms of action of molecular hydrogen and discuss modes of administration.
Here is a brief review of Dr. Antonucci's previous article on molecular hydrogen:
One of the primary mechanisms of action for molecular hydrogen is its ability to scavenge reactive oxygen species (ROS), such as superoxide anions, hydroxyl radicals, and peroxynitrite. These ROS are produced as byproducts of normal cellular metabolism and cellular death. ROS are also upregulated in many disease processes, having the ability to damage cells, genes, proteins, and tissues. The damage they cause to various cellular components, such as DNA, proteins, and lipids, leads to many issues, from grey hair to cancer and diseases like Alzheimer’s. By scavenging these ROS, molecular hydrogen can reduce cellular oxidative stress and protect against oxidative damage and disease.
In addition to its antioxidant properties, molecular hydrogen has also been found to have anti-inflammatory effects. It can reduce the expression of pro-inflammatory cytokines and chemokines such as TNF-alpha, IL-6, and MCP-1. This can help to mitigate the effects of chronic inflammation, which is implicated in allergies, brain injury, chronic pain, migraine, digestive issues, asthma, and the pathogenesis of many other diseases, including cancer.
Molecular hydrogen has also been found to regulate the expression of various genes and protein activation states and to modulate cellular signaling pathways, including the Nrf2/Keap1 pathway. This pathy regulates the expression of innate antioxidant and detoxification enzymes. It also enhances the AMP-activated protein kinase (AMPK) pathway, which regulates cellular energy metabolism. By modulating these genes and pathways, molecular hydrogen can promote cellular health and resilience (anti-aging).
To access the therapeutic effects of molecular hydrogen, it must be consumed in some form and reach target tissues (the brain, skin, muscles, digestive system, organs, etc.) There are several methods for consuming molecular hydrogen, all of which offer various advantages and disadvantages. However, before we begin discussing how to administer molecular hydrogen, it's important to be aware that, to date, no upper-safety (maximum) limit for H2 consumption has been established by regulatory agencies such as the US Food and Drug Administration (FDA). The US Food and Drug Administration has recognized hydrogen gas as a food additive, generally recognized as safe (GRAS) status. Hundreds of human studies for deep-sea diving have shown inhalation of hydrogen gas, at much greater amounts than what is used for therapeutic use, is well-tolerated by the body with no chronic or toxic effects. H2 has no known adverse effects or toxicity, even at high concentrations, and great efficacy on nearly all pathogenic states involved in oxidative stress and inflammation.
Another human study found that administering common doses of H2 (up to 4% H2 in air) for 60 minutes did not cause any adverse effects. However, longer-term studies are needed to assess higher doses' safety fully.
It is important to note that most studies on H2 consumption have used doses well below these levels and have generally found efficacy and no adverse effects. However, it is recommended that all individuals consult with a healthcare provider before consuming high doses of H2, especially for extended periods.
The minimal dose of inhaled molecular hydrogen that needs to be consumed for health benefits is still unclear. However, the proposed therapeutic dose for consumption seems to be about 80 mL hydrogen gas (6.6 mg or 3.3 mmol) per day, and maximum effects seem to occur after administration for one month. This aids in the calculation of dosing.
Molecular hydrogen can be generated through several processes. The most commonly used in low-volume medicine and commercial applications is through a molecular hydrogen generator, which uses electrolysis to break water into molecular hydrogen (H2) and oxygen (O). This process involves running a direct electrical current (DC) through the water and separating the molecular hydrogen gas from the oxygen gas. During the electrolysis process, water molecules are oxidized at the anode, which produces oxygen gas, and reduced at the cathode, which produces hydrogen gas.
The overall reaction is, therefore, known as a redox reaction. It is important to note that this requires pure water, also known as distilled water. Unless a Polymer Electrolyte Membrane (PEM) is utilized, impure/tap water can ruin the equipment and contaminate the reaction. Think of the PEM as a strainer. H2O is like pasta-water. Gravity is the flow of electricity. When you pour the pasta water into the strainer, the noodles stay, and the water selectively permeates and collects on the other side. This allows uni-directional selective passage of H2 through he membrane, so pure molecular hydrogen is collected.
The chemical equation for the electrolysis of water is:
2H2O(l)→ electricity→ 2H2(g) + O2(g)
The released molecular hydrogen and oxygen is a safe, pure gas form that can be inhaled, aerosolized, or suspended in a solution.
Another method of producing molecular hydrogen is a chemical reaction between water and elemental magnesium. When pure magnesium is placed in pure water at room temperature, the product of the reaction is magnesium hydroxide (MgOH2) and molecular hydrogen (H2). The reaction occurs slowly at room temperature and can be sped up by increasing the surface area of the magnesium (grinding it up), providing heat, or chemical catalysts and water-soluble acids that affect the pH (such as tartaric acid and adipic acid). It's also important to note that this is a slow reaction, taking approximately 10 minutes to begin and 20 minutes to conclude, even with catalysts. This method is more commonly used for creating hydrogen-rich water, which we will discuss later.
The chemical equation for this reaction is:
Mg(s) + 2H2O(l) → Mg(OH)2(s) + H2(g)
For large-scale industrial applications, molecular hydrogen can be produced by combining high-temperature steam [H2O(g)] with methane gas (CH4) under pressure. Catalysts of nickel or platinum are also used. The byproducts of this reaction are not exactly environmentally friendly, as it produces 3 H2 molecules and 1 molecule of carbon monoxide (CO).
The chemical equation for this reaction is:
CH4(g) + H2O(g)→pressure→ CO(g)+ 3H2(g)
Hydrogen is generally administered by one of four delivery routes: inhalation, ingesting hydrogen-enriched water, surface contact of hydrogen solutions, or injecting a sterile hydrogen-saturated saline solution. Each type of hydrogen administration has different pros and cons, speeds of action, and different primary effects on tissues.
One popular method of molecular hydrogen consumption is inhalation. This method primarily targets and benefits the respiratory and cardiovascular systems. When hydrogen gas is inhaled, because it is such a small and highly diffusable molecule, it can quickly enter the bloodstream through the lungs and reach the cells of various organs and tissues in the body. Inhaled hydrogen gas has been shown to have antioxidant and anti-inflammatory effects, and it has been studied for its potential therapeutic applications in various medical conditions. This makes it great for the co-treatment of lung infections, acute COVID, "long-COVID", asthma, COPD, allergies, atherosclerosis, heart disease, and more. This involves breathing molecular hydrogen via a dedicated inhaler or molecular hydrogen generator device.
Inhalation of hydrogen is typically performed by pumping hydrogen through a nasal cannula at 200-600 mL per minute, at a concentration of <4%. It is important to remember that humans require approximately 5 L of air per minute to breathe, so it is not advised to use a full face mask (non-rebreather mask) as one might use for oxygen administration.
Several methods exist to create H2-infused water, including infusing H2 gas into water under high pressure, electrolyzing water in a sealed container to produce and saturate the water with H2, and reacting magnesium metal or its hydride with water. These techniques can also be applied to other solvents besides water. H2 can penetrate glass and plastic containers quickly, but aluminum (and palladium) vessels can keep hydrogen gas for an extended period.
Hydrogen water generators range from $75 to $6,000, depending on the amount of hydrogen-rich water you wish to create. A small, inexpensive hydrogen water generator might be sufficient for personal use or traveling. A larger device is necessary if you would like your entire family or your patients to experience the benefits of hydrogen.
In the research, hydrogen water consumption has shown promising outcomes in many conditions such as Parkinson's Disease, Alzheimer's disease, autism, stroke, hypoxia-ischemia, concussion, diabetes/metabolic syndrome, high cholesterol and triglycerides, radiation side-effects, heart attack, atherosclerosis (hardening of arteries), liver disease, organ rejection (in transplants), NSAID-induced gastric lesions, acute pancreatitis, bladder pain, testicular injury, preeclampsia, acute noise-induced hearing loss, some retinal injuries, osteoporosis, periodontal diseases, joint diseases, and many more. Hydrogen could also be recognized as a possible anti-aging agent that tackles several hallmarks of aging, including loss of function and telomere length shortening.
Depending on the source, purity, and concentration of hydrogen in the water, most studies suggest drinking 1-2 liters a day. Notably, H2 concentrations as low as 0.08 ppm exhibited nearly the same effects as saturated HW (1.5 ppm H2), with very robust statistical differences compared to water controls. After HW is consumed, most H2 in the blood is undetectable within 30 min, likely due to lung expiration. Thus, how a low amount of HW over a short exposure period can be effective remains unknown. Kamimura and colleagues found that H2-water can accumulate in the liver with glycogen, which may partly explain this phenomenon. In another example, as a 4% gas, the amount of H2 exposed to a 60-kg person for 1 hour would be eight or more times higher than that of drinking saturated HW. Nevertheless, HW is shown to be as effective as, sometimes more effective than, inhaled H2. Therefore, the amount of administered H2 seems independent of the magnitude of effects in many cases. Perhaps the mode of delivery is more important than we have realized.
One argument often made regarding hydrogen water studies is that merely increasing water consumption will confer significant health benefits and that even mild dehydration can contribute to various illnesses. However, that argument is invalid when considering the studies comparing hydrogen water to the same amount of plain water consumed.
Hydrogen water's primary concern is its price, which poses a significant challenge to adoption. Due to the packaging difficulties, a single can or bottle of hydrogen water costs between $2.50 and $4.00, compared to approximately $0.70 for bottled water. In many published studies, the participants consumed 51 ounces of hydrogen water daily, equivalent to almost seven 8-ounce bottles (up to $28). Hydrogen water tablets and machines are also accessible and may offer some cost savings.
Certain manufacturers with extensive knowledge of packaging and chemistry, such as HydroShot®, have produced a proprietary and researched super-saturated H2 drink with a full day's dosage of H2 in one drink. This would allow a one-per-day consumption. The retail cost of this product is approximately $40 for 12. This link will save you 10% compliments of a partnership with the Carrick Institute.
Another method of molecular hydrogen consumption is through topical applications; this involves saturating a topical solution such as liquid (baths/eye drops), cream, or gel with molecular hydrogen gas before applying it to the skin. This technique has been studied for potential therapeutic applications in psoriasis, cracks and ulcers, burns and scalds, corns and calluses, herpetic lesions (cold sores), acne, etc. wrinkles, sun damage, and more.
Hydrogen bathing is also an option, which involves soaking in water infused with molecular hydrogen gas. In studies, subjects bathed in hydrogen-rich 41ºC (106ºF) water for 10 minutes, once per day, for six months.
Hydrogen gas has been shown to affect the skin and enter the bloodstream, which can help neutralize harmful free radicals and reduce oxidative stress. When the body is exposed to hydrogen gas, it can potentially help to activate certain cellular pathways that promote cellular repair and regeneration. This can potentially lead to improved skin health and a reduction in the appearance of wrinkles and fine lines. Bathing in hydrogen-rich water has been shown to help reduce muscle soreness and fatigue after exercise, which can help improve recovery time and increase overall energy levels. Additionally, hydrogen bathing has been shown to normalize skin pigmentation, reduce visceral fat, and improve blood glucose metabolism.
Results reported that "wide-ranging, dense, and irregularly shaped skin blotches became markedly smaller and thinner, assumedly through reductive bleaching of melanin and lipofuscin and promotion of dermal cell renewal by the hydrogen-rich warm water. Ultrasonic resonance-based analysis on the abdominal cross-section revealed that the visceral fat area decreased from 47 to 36 cm2 (-23%), and the abdominal circumference decreased from 91 to 82 cm (-10%) in the two female subjects bathing in hydrogen water. Also, after 6-month hydrogen-water bathing, the low-density lipoprotein cholesterol level was decreased by 16.2%, and the fasting blood glucose level increased by 13.6% in the blood of a female subject.
One way to prepare this sterile isotonic solution for injection or infusion in place of normal saline is to immerse saline bags in a hydrogen bath. The permeability of the plastic bags containing the hydrogen allows the hydrogen to diffuse out of the hydrogen bath into the saline fluid over approximately 4 hours. The newly formed hydrogen solution must be infused within 1 hour for maximum benefits.
It is possible to use isotonic solutions dissolved with hydrogen for an intravenous and/or local injection. This allows for direct administration and fine control over the dosage if desired.
Only licensed and qualified medical professionals should perform intravenous or injections.
Even though we know so much about molecular hydrogen and its health benefits, clinicians are researchers are still trying to understand it. We have yet to elucidate the exact mechanisms by which hydrogen causes its health effects. For example, a healthy individual's gut bacteria produces approximately 10-12 L of hydrogen daily (on the order of 10-100x, the amount consumed in studies). So why does consuming small doses of exogenous hydrogen cause such profound effects?
H2 infusion is limited to 0.8 mM under normal pressure, and drinking H2-water only results in a blood H2 concentration of 10 μM with a short duration in the body. Additionally, inhaling 1-4% of H2 gas for 30 minutes or more is more effective, resulting in a blood concentration of 8-32 μM. However, theoretically, these levels should not be enough to fully exhibit the benefits of H2 that we observe due to the slow direct reaction rate of H2 with -OH in water. So why do such low levels of H2 effectively compete with numerous cellular targets in chronic or acute disease processes?
Despite these questions and uncertainties, studies still show that H2 can regulate gene expression and signal transductions, resulting in various phenotypes, such as reducing inflammation, stimulating energy metabolism, and neuroprotection. So, regardless of how it is consumed, even small doses may offer therapeutic effects on our health and well-being.
A concussion is a mild traumatic brain injury (TBI) that can cause a range of challenges, including physical, emotional, autonomic, vestibular, oculomotor, sleep, and cognitive problems, along with a myriad of other symptoms. Despite the common perception that sports cause most concussions, only about 1 in 7 are sports-related. Instead, other injuries, such as falls, motor vehicle accidents, and assaults, are more likely to cause concussions. Although most people recover within a few weeks, some may experience persistent symptoms lasting for months or even years. See: "Does Everyone Recover From a Concussion?"
Recent research has shown that molecular hydrogen (H2) has potential therapeutic effects on various neurological conditions, including traumatic brain injury. H2 is a colorless, odorless, and tasteless gas studied for its antioxidant, anti-inflammatory, and anti-apoptotic properties. This article will explore how molecular hydrogen can benefit concussions and promote recovery.
Molecular hydrogen is the smallest molecule in the universe and has potent antioxidant, anti-inflammatory, and neuroprotective properties. These properties make it an attractive candidate for treating various conditions, including diabetes, heart disease, and neurological disorders. In recent years, there has been growing interest in the potential of molecular hydrogen to benefit concussion patients.
Molecular hydrogen has been studied for its potential therapeutic effects on various health conditions for decades. However, its use as a medical therapy is relatively recent, with the first clinical trials conducted in the early 2000s. One of the earliest reports of the medical use of molecular hydrogen was in 1975, when it was first used to treat decompression sickness in deep-sea divers. This condition, also known as the bends, occurs when nitrogen gas bubbles form in the blood vessels and tissues due to rapid decompression, sometimes causing severe pain, possible death, and other symptoms. Hydrogen was used as a therapeutic gas to reduce the severity of the symptoms and improve outcomes in affected divers. Since that time, research on the medical applications of molecular hydrogen has expanded to include a wide range of health conditions, including but not limited to neurological disorders, cardiovascular diseases, metabolic disorders, and cancer.
Hydrogen has antioxidant and anti-inflammatory effects that dampen oxidative stress and inflammation, accompanying nearly every disease affecting all humans. Another "out of this world" issue caused by oxidative stress is neurological deficits and long-term health issues caused by space travel. New research suggests that a little as one hour of space radiation causes damaging levels of oxidative stress, which compromises thinking and decision-making and is one of the greatest challenges for space travel.
Excessive amounts of reactive oxygen species (ROS) can damage the composition of mitochondrial electron transport chains, disrupt intracellular redox systems, and lead to lipid peroxidation, protein misfolding, and DNA strand breakage. This can trigger oxidative stress, activate the JNK signaling system, up-regulate pro-oxidant genes, and inhibit antioxidants associated with nuclear factor-e2 related factor (Nrf2). As a result, matrix metalloproteinases (MMP) can be induced, along with the secretion of inflammatory chemokines such as tumor necrosis factors (TNFs), interleukin (IL)−1, IL-6, and IL-8, leading to inflammation. Additionally, peroxidation and inflammation can promote cell apoptosis. This can subsequently result in the release of pro-fibrotic cytokines like platelet-derived growth factors (PDGFs), insulin-like growth factors (IGFs), and basic fibroblast growth factors (FGFs), which can promote the differentiation of monocytes into M2 macrophages, enhance fibroblast proliferation and differentiation into myofibroblasts, and amplify inflammation.
One of the primary mechanisms by which molecular hydrogen can benefit a concussion is its ability to reduce oxidative stress. Molecular hydrogen helps mitigate this damage by neutralizing free radicals and, in effect, reducing inflammatory processes in the body along with other tissue stressors.
Oxidative stress occurs when there is an imbalance between the production of free radicals and the body's ability to neutralize them with antioxidants. Overwhelming a person's ability to clear or reduce these harmful interactions in the body can lead to cellular damage and inflammation, worsening the effects of a concussion.
As detailed in "A Simple Guide to a Not-So-Simple Concussion", oxidative stress is a common feature of concussion; it can cause damage to neurons and other brain cells. Several studies have demonstrated the antioxidant effects of molecular hydrogen in animal models of traumatic brain injury. For example, a study published in the journal Brain Research showed that rats exposed to a concussive impact had significantly lower levels of oxidative stress markers in their brains when treated with molecular hydrogen gas.
At the same time, H2 has been shown to activate the Nrf2 pathway, a cellular signaling pathway that regulates antioxidant and anti-inflammatory responses, which can scavenge free radicals and reduce oxidative stress in the brain. By reducing oxidative stress and inflammation, H2 can protect brain cells from further damage and promote recovery after a concussion.
Molecular hydrogen can neutralize free radicals, molecules that can cause oxidative damage, thus reducing oxidative stress. It also leads to upregulating antioxidant enzymes, such as superoxide dismutase (SOD) and catalase. Properly using molecular hydrogen can help protect brain cells and promote healing more than the consumption of any known "superfood".
Another pathway in which molecular hydrogen can benefit concussion patients is through its anti-inflammatory properties. In the case of concussions, the inflammatory response can exacerbate the damage to the brain and prolong the recovery process. Studies have shown that H2 can reduce inflammation in the brain by inhibiting the production of pro-inflammatory cytokines and chemokines. These signaling molecules recruit immune cells to the injury site and promote inflammation. H2 has been shown to reduce the levels of these molecules in animal models of traumatic brain injury, leading to a reduction in inflammation and improved neurological function. By reducing inflammation, molecular hydrogen can help to minimize the damage caused by a concussion.
Inflammation is a natural response of the immune system to injury or infection. Excessive or prolonged inflammation can lead to tissue damage and cell death.
The hydrogen molecule, despite being a weak reducing agent and having a low molecular weight, has the ability to diffuse quickly and pass through cell membranes and lipid bilayers. It can then target the cell nuclei and mitochondria, where there is an abundance of reactive oxygen species (ROS), and selectively neutralize highly reactive toxic ROS, such as -OH. Recent studies have also shown that hydrogen has a positive effect on the Nrf2 pathway, which is a crucial regulator of electrophilic/antioxidant homeostasis and helps maintain the functional integrity of cells during oxidative stress conditions. Hydrogen activates the Nrf2-Keap1 system, triggers the activation of antioxidant response elements (AREs), and promotes the expression of multiple cytoprotective proteins, including glutathione, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase, and heme-1 oxygenase. It also activates the transcription factor FoxO1, reduces the damage of -OH to mitochondria, and inhibits the overproduction of ROS. Additionally, hydrogen inhibits the infiltration of phagocytes to sites of inflammation, thereby preventing the subsequent release of reactive substances, and down-regulates various pro-inflammatory and inflammatory cytokines such as interleukin (IL)-1β, IL-6, TNF-α, and intracellular adhesion molecules (ICAM)-1, thus achieving an anti-inflammatory effect. Moreover, hydrogen also weakens abnormal expression of miRNA associated with brain injury.
Following a concussion, there is often an energy imbalance caused by a decrease in glucose uptake by neurological tissue. Glucose is critical in the production of a cellular energy molecule called ATP. If a brain cell cannot access glucose, it cannot make ATP, leading to cell death and neurological dysfunction. Molecular hydrogen may mitigate this by increasing glucose uptake and providing a supplemental fuel source for mitochondria to produce ATP in the brain.
One of the unique properties of molecular hydrogen is its ability to penetrate cell membranes and reach the mitochondria, which are the cell's powerhouses. Mitochondrial dysfunction is a common feature of TBI. It can contribute to developing symptoms such as fatigue and cognitive impairment. By reaching the mitochondria, molecular hydrogen can help to restore their function and promote healing. Several studies have shown that molecular hydrogen can improve energy metabolism in the brain. For example, a study published in the journal Medical Gas Research found that rats treated with molecular hydrogen had higher brain ATP levels than untreated rats.
Molecular hydrogen has also been shown to have a neuroprotective effect. In animal studies, molecular hydrogen has been shown to protect against neuronal damage and cell death.
Apoptosis is programmed cell death that occurs in response to injury or stress. Excessive apoptosis can lead to cell death and tissue damage. H2 has been shown to inhibit apoptosis in the brain by regulating the expression of pro- and anti-apoptotic proteins such as BCL-2 and caspase-3. In animal models of traumatic brain injury, H2 has been shown to reduce apoptosis in the brain and improve neurological function.
Hydrogen exhibits cytoprotective properties that improve cell apoptosis. Apoptosis plays a crucial role in the progression of concussion-related brain injury. By significantly inhibiting the ectopic expression of the death promoter Bcl-2 related X protein (bax) and the expression of caspase-3, while promoting the expression of the anti-apoptotic protein Bcl-2, hydrogen can effectively provide cytoprotection.
Hydrogen also enhances blood perfusion and reduces vascular damage caused by concussion. Vascular injury and endothelial dysfunction are key factors in the development of traumatic brain injury. Excitotoxic brain activity and metabolic failure leads to the excessive production of reactive oxygen species (ROS) and the depletion of vascular protectant nitric oxide (NO) within a few minutes, resulting in the nitrosylation of protein tyrosine residues and lipid peroxidation. This ultimately weakens the vasomotor response, causing vascular stenosis. Furthermore, after concussion, NADPH oxidases (NOXs), especially NOX2 and NOX4, which are abundantly expressed in vascular endothelial cells, are up-regulated, leading to excessive production of ROS, changes in calcium homeostasis, calcium metabolism disorders, and triggering antifibrinolysis-coagulation cascade action, ultimately leading to blood clotting and vascular occlusion. Hydrogen helps to alleviate these effects.
The available evidence suggests that hydrogen exerts a protective effect on damaged blood vessels and improves blood perfusion. It achieves this by various mechanisms such as inhibiting the degradation of cyclic guanosine monophosphate (cGMP) through phosphodiesterase, thereby increasing cGMP levels and promoting protein kinase activation. Additionally, hydrogen increases intracellular calcium levels and stimulates vascular endothelial growth factors to enhance nitric oxide production. Moreover, hydrogen opens the potassium channel sensitive to ATP and activates downstream mitogen-activated protein kinase pathways, which promote angiogenesis. Experimental studies also demonstrate that hydrogen prevents arterial intimal hyperplasia and atherosclerosis by inhibiting ROS and TNF-α/NF-κB pathways, as well as foam cell apoptosis derived from macrophages. It stabilizes atherosclerotic plaques, reduces vascular stenosis, and promotes the formation of vascular collaterals using the FIk1-Notch signal stimulated by paracrine VEGFs to improve local microcirculation.
While halting brain cell death is paramount in concussion, promoting survivability and growth of healthy cells may be equally important in full recovery. H2 has been shown to enhance the production of brain-derived neurotrophic factor (BDNF). This protein promotes the growth and survival of neurons. BDNF is essential for neuroplasticity, development, and the maintenance of the nervous system. Its dysfunction has been implicated in neurological disorders, including traumatic brain injury. By enhancing BDNF production, H2 may promote the growth and survival of brain cells and potentially improve recovery after a concussion.
This protein, BDNF, promotes the growth and survival of neurons. BDNF is essential for neuroplasticity, development, and the maintenance of the nervous system. Its dysfunction has been implicated in neurological disorders, including traumatic brain injury.
Concussions can cause various cognitive impairments, including but not limited to memory loss, attention deficits, and executive dysfunction. H2 may benefit concussions by improving cognitive function through its anti-inflammatory and neuroprotective effects. A 2019 study published in the journal Frontiers in Neuroscience found that mice treated with molecular hydrogen after a traumatic brain injury had improved cognitive function and reduced levels of inflammation compared to untreated mice. Another study in the journal Neuroscience Letters in 2012 aimed to investigate the potential therapeutic effects of H2 on cognitive function in a rat model of blast-induced traumatic brain injury.
The researchers exposed adult male rats to a single blast wave generated by a shock tube. The rats were then randomly divided into control and H2 treatment groups. The H2 treatment group received H2 gas at a concentration of 2% for one hour per day for seven consecutive days, while the control group received room air.
The researchers assessed the cognitive function of the rats using the Morris water maze test, a widely used test of spatial learning and memory. The results showed that the rats in the H2 treatment group performed better on the Morris water maze test than those in the control group. The H2-treated rats showed shorter escape latencies and swam shorter distances to reach the hidden platform, indicating improved spatial learning and memory.
The Morris Water Maze test involves placing the rats in a pool of water and measuring the time it takes them to find a hidden platform. The rats are trained on the task over several days, and their performance is evaluated based on the time they take to find the platform and the distance they swim.
In addition to the Morris water maze test, the researchers also evaluated the rats' brains' oxidative stress and inflammation levels. They found that H2 treatment reduced oxidative stress markers and pro-inflammatory cytokines in the brain, suggesting that H2 may have anti-inflammatory and antioxidant effects that could protect the brain from damage.
For the same reasons that H2 might benefit a patient that has sustained a concussion, molecular hydrogen may also help healthy individuals. Research has shown that H2 may also:
With all these benefits, you may wonder how hydrogen is administered. Molecular hydrogen (H2) can be administered in several ways, depending on the individual's intended use and preferences. Here are some common ways to administer H2:
We discuss the pros and cons of each method of administration in a future article.
In summary, molecular hydrogen is a simple yet effective way to aid recovery from concussion and promote optimal health and quality of life.
Dr. Antonucci utilizes molecular hydrogen at his home (daily) for health maintenance. He also offers access to this contemporary intervention to his patients.
Updated 3.27.23: Per request, I added more in-depth explanations for clinicians - MMA