Special Issue "Oxygen Therapy"

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (30 April 2021).

Special Issue Editors

Prof. Uri Ashery
E-Mail Website
Guest Editor
Sagol School of Neuroscience, School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv, Israel
Interests: synaptic transmission; synaptic plsaticity; super resolution microscopy; neurodegenerative diseases; Alzheimer’s disease; Parkinson’s disease
Prof. Shai Efrati
E-Mail Website
Guest Editor
1. Sagol Center for Hyperbaric Medicine and Research, Shamir (Assaf-Harofeh) Medical Center, Israel
2. Sackler School of Medicine and Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel
Interests: regeneration; brain; hyperbaric medicine; physiology
Dr. Ronit Shapira
E-Mail Website
Assistant Guest Editor
School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv, Israel
Interests: hyperbaric oxygen therapy; Alzheimer’s diseas; neurodegenerative diseases

Special Issue Information

Dear Colleagues,

Oxygen is vital for normal cell metabolism. Oxygen therapy is the use of oxygen as a medical treatment. Air usually consists of 21% oxygen by volume, while oxygen therapy increases oxygen by up to 100% or increases oxygen solubility in the blood and tissues by elevating atmospheric pressure. The use of oxygen in the clinic is common for centuries and is considered one of the most effective and safe medicines needed in health systems, according to the World Health Organization's List of Essential Medicines. In order to increase oxygen-delivered dosages and their relative concentrations, the environmental pressure can be increased. For example, to enhance the amount of oxygen dissolved in the body’s tissues, hyperbaric oxygen therapy (HBOT) including the inhalation of 100% oxygen at pressures exceeding one atmosphere absolute (1 ATA) needs to be used. Historically, HBOT has been applied worldwide, mostly for chronic non-healing wounds. In recent years, growing evidence related to the regenerative effects of HBOT has emerged. The combined action of both hyperoxia and hyperbaric pressure leads to significant improvement in tissue oxygenation while targeting both oxygen and pressure-sensitive genes, resulting in improved mitochondrial metabolism with anti-apoptotic and anti-inflammatory effects. Moreover, the intermittent increase of oxygen concentration activates many of the mediators and cellular pathways that are usually induced by hypoxia but not hazardous hypoxia—termed the hyperoxic–hypoxic paradox. Among others, the intermittent hyperoxic exposure during HBOT can affect the levels of hypoxia-inducible factor 1-alpha (HIF-1a), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) activity, induce stem cell proliferation, augment circulating levels of endothelial progenitor cells (EPCs) and angiogenesis factors, as well as induce angiogenesis and improve blood flow. In addition to the stimulation of EPCs, HBOT can decrease the inflammatory response in endothelial cells mediated by TNF-alpha, and thus promote vascular recovery. Recently, HBOT also been shown to improve acute neurological conditions like stroke and traumatic brain injury and alleviates chronic conditions such as vascular dementia. In addition, both animal and human studies have demonstrated the beneficial effects of HBOT on mitochondrial function.

This Special Issue, entitled “Oxygen Therapy”, will feature exciting novel studies in this area as well as stimulate new avenues of research into the biological functions of oxygen and the hyperoxic–hypoxic paradox, its underlying mechanisms, and the potential application of its use as a novel therapeutic approach.

Prof. Uri Ashery
Prof. Shai Efrati
Dr. Ronit Shapira
Guest Editors

Manuscript Submission Information

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Keywords

  • Hyperbaric oxygen therapy
  • Hyperoxic–hypoxic paradox
  • Mitochondria
  • Tissue regeneration
  • Angiogenesis
  • Neurogenesis
  • Anti-inflammation
  • Stem cells
  • Brain injury
  • Brain disorders
  • Epigenetic

Published Papers (9 papers)

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Research

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Article
Oxygen: The Rate-Limiting Factor for Episodic Memory Performance, Even in Healthy Young Individuals
Biomolecules 2020, 10(9), 1328; https://doi.org/10.3390/biom10091328 - 17 Sep 2020
Cited by 1 | Viewed by 1295
Abstract
Cognition is a crucial element of human functionality. Like any other physical capability, cognition is both enabled and limited by tissue biology. The aim of this study was to investigate whether oxygen is a rate-limiting factor for any of the main cognitive domains [...] Read more.
Cognition is a crucial element of human functionality. Like any other physical capability, cognition is both enabled and limited by tissue biology. The aim of this study was to investigate whether oxygen is a rate-limiting factor for any of the main cognitive domains in healthy young individuals. Fifty-six subjects were randomly assigned to either increased oxygen supply using hyperbaric oxygen (two atmospheres of 100% oxygen) or to a “sham” treatment (a simulation of increased pressure in a chamber with normal air). While in the chamber, participants went through a battery of tests evaluating the major cognitive domains including information processing speed, episodic memory, working memory, cognitive flexibility, and attention. The results demonstrated that from all evaluated cognitive domains, a statistically significant improvement was found in the episodic memory of the hyper-oxygenized group. The hyper-oxygenized group demonstrated a better learning curve and a higher resilience to interference. To conclude, oxygen delivery is a rate-limiting factor for memory function even in healthy young individuals under normal conditions. Understanding the biological limitations of our cognitive functions is important for future development of interventional tools that can be used in daily clinical practice. Full article
(This article belongs to the Special Issue Oxygen Therapy)
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Article
Hyperoxia Alters Ultrastructure and Induces Apoptosis in Leukemia Cell Lines
Biomolecules 2020, 10(2), 282; https://doi.org/10.3390/biom10020282 - 12 Feb 2020
Cited by 4 | Viewed by 1175
Abstract
Oxygenation conditions are crucial for growth and tumor progression. Recent data suggests a decrease in cancer cell proliferation occurring after exposure to normobaric hyperoxia. Those changes are associated with fractal dimension. The purpose of this research was to study the impact of hyperoxia [...] Read more.
Oxygenation conditions are crucial for growth and tumor progression. Recent data suggests a decrease in cancer cell proliferation occurring after exposure to normobaric hyperoxia. Those changes are associated with fractal dimension. The purpose of this research was to study the impact of hyperoxia on apoptosis and morphology of leukemia cell lines. Two hematopoietic lymphoid cancer cell lines (a T-lymphoblastoid line, JURKAT and a B lymphoid line, CCRF-SB) were tested under conditions of normobaric hyperoxia (FiO2 > 60%, ± 18h) and compared to a standard group (FiO2 = 21%). We tested for apoptosis using a caspase-3 assay. Cell morphology was evaluated by cytospin, microphotography after coloration, and analysis by a fractal dimension calculation software. Our results showed that exposure of cell cultures to transient normobaric hyperoxia induced apoptosis (elevated caspase-3) as well as significant and precocious modifications in cell complexity, as highlighted by increased fractal dimensions in both cell lines. These features are associated with changes in structure (pycnotic nucleus and apoptosis) recorded by microscopic analysis. Such morphological alterations could be due to several molecular mechanisms and rearrangements in the cancer cell, leading to cell cycle inhibition and apoptosis as shown by caspase-3 activity. T cells seem less resistant to hyperoxia than B cells. Full article
(This article belongs to the Special Issue Oxygen Therapy)
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Review

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Review
Hyperbaric Oxygen Treatment: Effects on Mitochondrial Function and Oxidative Stress
Biomolecules 2021, 11(12), 1827; https://doi.org/10.3390/biom11121827 - 03 Dec 2021
Viewed by 526
Abstract
Hyperbaric oxygen treatment (HBOT)—the administration of 100% oxygen at atmospheric pressure (ATA) greater than 1 ATA—increases the proportion of dissolved oxygen in the blood five- to twenty-fold. This increase in accessible oxygen places the mitochondrion—the organelle that consumes most of the oxygen that [...] Read more.
Hyperbaric oxygen treatment (HBOT)—the administration of 100% oxygen at atmospheric pressure (ATA) greater than 1 ATA—increases the proportion of dissolved oxygen in the blood five- to twenty-fold. This increase in accessible oxygen places the mitochondrion—the organelle that consumes most of the oxygen that we breathe—at the epicenter of HBOT’s effects. As the mitochondrion is also a major site for the production of reactive oxygen species (ROS), it is possible that HBOT will increase also oxidative stress. Depending on the conditions of the HBO treatment (duration, pressure, umber of treatments), short-term treatments have been shown to have deleterious effects on both mitochondrial activity and production of ROS. Long-term treatment, on the other hand, improves mitochondrial activity and leads to a decrease in ROS levels, partially due to the effects of HBOT, which increases antioxidant defense mechanisms. Many diseases and conditions are characterized by mitochondrial dysfunction and imbalance between ROS and antioxidant scavengers, suggesting potential therapeutic intervention for HBOT. In the present review, we will present current views on the effects of HBOT on mitochondrial function and oxidative stress, the interplay between them and the implications for several diseases. Full article
(This article belongs to the Special Issue Oxygen Therapy)
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Review
Hyperbaric Oxygen Treatment—From Mechanisms to Cognitive Improvement
Biomolecules 2021, 11(10), 1520; https://doi.org/10.3390/biom11101520 - 15 Oct 2021
Cited by 1 | Viewed by 461
Abstract
Hyperbaric oxygen treatment (HBOT)—the medical use of oxygen at environmental pressure greater than one atmosphere absolute—is a very effective therapy for several approved clinical situations, such as carbon monoxide intoxication, incurable diabetes or radiation-injury wounds, and smoke inhalation. In recent years, it has [...] Read more.
Hyperbaric oxygen treatment (HBOT)—the medical use of oxygen at environmental pressure greater than one atmosphere absolute—is a very effective therapy for several approved clinical situations, such as carbon monoxide intoxication, incurable diabetes or radiation-injury wounds, and smoke inhalation. In recent years, it has also been used to improve cognition, neuro-wellness, and quality of life following brain trauma and stroke. This opens new avenues for the elderly, including the treatment of neurological and neurodegenerative diseases and improvement of cognition and brain metabolism in cases of mild cognitive impairment. Alongside its integration into clinics, basic research studies have elucidated HBOT’s mechanisms of action and its effects on cellular processes, transcription factors, mitochondrial function, oxidative stress, and inflammation. Therefore, HBOT is becoming a major player in 21st century research and clinical treatments. The following review will discuss the basic mechanisms of HBOT, and its effects on cellular processes, cognition, and brain disorders. Full article
(This article belongs to the Special Issue Oxygen Therapy)
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Review
The Effects of Hyperbaric Oxygenation on Oxidative Stress, Inflammation and Angiogenesis
Biomolecules 2021, 11(8), 1210; https://doi.org/10.3390/biom11081210 - 14 Aug 2021
Cited by 2 | Viewed by 1038
Abstract
Hyperbaric oxygen therapy (HBOT) is commonly used as treatment in several diseases, such as non-healing chronic wounds, late radiation injuries and carbon monoxide poisoning. Ongoing research into HBOT has shown that preconditioning for surgery is a potential new treatment application, which may reduce [...] Read more.
Hyperbaric oxygen therapy (HBOT) is commonly used as treatment in several diseases, such as non-healing chronic wounds, late radiation injuries and carbon monoxide poisoning. Ongoing research into HBOT has shown that preconditioning for surgery is a potential new treatment application, which may reduce complication rates and hospital stay. In this review, the effect of HBOT on oxidative stress, inflammation and angiogenesis is investigated to better understand the potential mechanisms underlying preconditioning for surgery using HBOT. A systematic search was conducted to retrieve studies measuring markers of oxidative stress, inflammation, or angiogenesis in humans. Analysis of the included studies showed that HBOT-induced oxidative stress reduces the concentrations of pro-inflammatory acute phase proteins, interleukins and cytokines and increases growth factors and other pro-angiogenesis cytokines. Several articles only noted this surge after the first HBOT session or for a short duration after each session. The anti-inflammatory status following HBOT may be mediated by hyperoxia interfering with NF-κB and IκBα. Further research into the effect of HBOT on inflammation and angiogenesis is needed to determine the implications of these findings for clinical practice. Full article
(This article belongs to the Special Issue Oxygen Therapy)
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Review
An Extra Breath of Fresh Air: Hyperbaric Oxygenation as a Stroke Therapeutic
Biomolecules 2020, 10(9), 1279; https://doi.org/10.3390/biom10091279 - 04 Sep 2020
Cited by 4 | Viewed by 1749
Abstract
Stroke serves as a life-threatening disease and continues to face many challenges in the development of safe and effective therapeutic options. The use of hyperbaric oxygen therapy (HBOT) demonstrates pre-clinical effectiveness for the treatment of acute ischemic stroke and reports reductions in oxidative [...] Read more.
Stroke serves as a life-threatening disease and continues to face many challenges in the development of safe and effective therapeutic options. The use of hyperbaric oxygen therapy (HBOT) demonstrates pre-clinical effectiveness for the treatment of acute ischemic stroke and reports reductions in oxidative stress, inflammation, and neural apoptosis. These pathophysiological benefits contribute to improved functional recovery. Current pre-clinical and clinical studies are testing the applications of HBOT for stroke neuroprotection, including its use as a preconditioning regimen. Mild oxidative stress may be able to prime the brain to tolerate full extensive oxidative stress that occurs during a stroke, and HBOT preconditioning has displayed efficacy in establishing such ischemic tolerance. In this review, evidence on the use of HBOT following an ischemic stroke is examined, and the potential for HBOT preconditioning as a neuroprotective strategy. Additionally, HBOT as a stem cell preconditioning is also discussed as a promising strategy, thus maximizing the use of HBOT for ischemic stroke. Full article
(This article belongs to the Special Issue Oxygen Therapy)
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Review
Molecular and Therapeutic Aspects of Hyperbaric Oxygen Therapy in Neurological Conditions
Biomolecules 2020, 10(9), 1247; https://doi.org/10.3390/biom10091247 - 27 Aug 2020
Cited by 4 | Viewed by 1914
Abstract
In hyperbaric oxygen therapy (HBOT), the subject is placed in a chamber containing 100% oxygen gas at a pressure of more than one atmosphere absolute. This treatment is used to hasten tissue recovery and improve its physiological aspects, by providing an increased supply [...] Read more.
In hyperbaric oxygen therapy (HBOT), the subject is placed in a chamber containing 100% oxygen gas at a pressure of more than one atmosphere absolute. This treatment is used to hasten tissue recovery and improve its physiological aspects, by providing an increased supply of oxygen to the damaged tissue. In this review, we discuss the consequences of hypoxia, as well as the molecular and physiological processes that occur in subjects exposed to HBOT. We discuss the efficacy of HBOT in treating neurological conditions and neurodevelopmental disorders in both humans and animal models. We summarize by discussing the challenges in this field, and explore future directions that will allow the scientific community to better understand the molecular aspects and applications of HBOT for a wide variety of neurological conditions. Full article
(This article belongs to the Special Issue Oxygen Therapy)
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Review
The Hyperoxic-Hypoxic Paradox
Biomolecules 2020, 10(6), 958; https://doi.org/10.3390/biom10060958 - 25 Jun 2020
Cited by 23 | Viewed by 3753
Abstract
Effective metabolism is highly dependent on a narrow therapeutic range of oxygen. Accordingly, low levels of oxygen, or hypoxia, are one of the most powerful inducers of gene expression, metabolic changes, and regenerative processes, including angiogenesis and stimulation of stem cell proliferation, migration, [...] Read more.
Effective metabolism is highly dependent on a narrow therapeutic range of oxygen. Accordingly, low levels of oxygen, or hypoxia, are one of the most powerful inducers of gene expression, metabolic changes, and regenerative processes, including angiogenesis and stimulation of stem cell proliferation, migration, and differentiation. The sensing of decreased oxygen levels (hypoxia) or increased oxygen levels (hyperoxia), occurs through specialized chemoreceptor cells and metabolic changes at the cellular level, which regulate the response. Interestingly, fluctuations in the free oxygen concentration rather than the absolute level of oxygen can be interpreted at the cellular level as a lack of oxygen. Thus, repeated intermittent hyperoxia can induce many of the mediators and cellular mechanisms that are usually induced during hypoxia. This is called the hyperoxic-hypoxic paradox (HHP). This article reviews oxygen physiology, the main cellular processes triggered by hypoxia, and the cascade of events triggered by the HHP. Full article
(This article belongs to the Special Issue Oxygen Therapy)
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Other

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Commentary
Molecular Biomarkers of Oxygen Therapy in Patients with Diabetic Foot Ulcers
Biomolecules 2021, 11(7), 925; https://doi.org/10.3390/biom11070925 - 22 Jun 2021
Cited by 2 | Viewed by 990
Abstract
Hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT) including continuous diffuse oxygen therapy (CDOT) are often utilized to enhance wound healing in patients with diabetic foot ulcerations. High pressure pure oxygen assists in the oxygenation of hypoxic wounds to increase perfusion. Although [...] Read more.
Hyperbaric oxygen therapy (HBOT) and topical oxygen therapy (TOT) including continuous diffuse oxygen therapy (CDOT) are often utilized to enhance wound healing in patients with diabetic foot ulcerations. High pressure pure oxygen assists in the oxygenation of hypoxic wounds to increase perfusion. Although oxygen therapy provides wound healing benefits to some patients with diabetic foot ulcers, it is currently performed from clinical examination and imaging. Data suggest that oxygen therapy promotes wound healing via angiogenesis, the creation of new blood vessels. Molecular biomarkers relating to tissue inflammation, repair, and healing have been identified. Predictive biomarkers can be used to identify patients who will most likely benefit from this specialized treatment. In diabetic foot ulcerations, specifically, certain biomarkers have been linked to factors involving angiogenesis and inflammation, two crucial aspects of wound healing. In this review, the mechanism of how oxygen works in wound healing on a physiological basis, such as cell metabolism and growth factor signaling transduction is detailed. Additionally, observable clinical outcomes such as collagen formation, angiogenesis, respiratory burst and cell proliferation are described. The scientific evidence for the impact of oxygen on biomolecular pathways and its relationship to the outcomes in clinical research is discussed in this narrative review. Full article
(This article belongs to the Special Issue Oxygen Therapy)
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