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Ageing Research Reviews Jul 2021The absolute reliance of the mammalian brain on oxygen to generate ATP renders it acutely vulnerable to hypoxia, whether at high altitude or in clinical settings of... (Review)
Review
The absolute reliance of the mammalian brain on oxygen to generate ATP renders it acutely vulnerable to hypoxia, whether at high altitude or in clinical settings of anemia or pulmonary disease. Hypoxia is pivotal to the pathogeneses of myriad neurological disorders, including Alzheimer's, Parkinson's and other age-related neurodegenerative diseases. Conversely, reduced environmental oxygen, e.g. sojourns or residing at high altitudes, may impart favorable effects on aging and mortality. Moreover, controlled hypoxia exposure may represent a treatment strategy for age-related neurological disorders. This review discusses evidence of hypoxia's beneficial vs. detrimental impacts on the aging brain and the molecular mechanisms that mediate these divergent effects. It draws upon an extensive literature search on the effects of hypoxia/altitude on brain aging, and detailed analysis of all identified studies directly comparing brain responses to hypoxia in young vs. aged humans or rodents. Special attention is directed toward the risks vs. benefits of hypoxia exposure to the elderly, and potential therapeutic applications of hypoxia for neurodegenerative diseases. Finally, important questions for future research are discussed.
Topics: Aged; Humans; Aging; Brain; Hypoxia; Neuroprotection
PubMed: 33862277
DOI: 10.1016/j.arr.2021.101343 -
The New England Journal of Medicine Feb 2011
Review
Topics: Adaptive Immunity; Animals; Basic Helix-Loop-Helix Transcription Factors; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Immunity, Innate; Infections; Inflammation; Inflammatory Bowel Diseases; Neoplasms; Procollagen-Proline Dioxygenase; Signal Transduction
PubMed: 21323543
DOI: 10.1056/NEJMra0910283 -
Nature Reviews. Cancer Jun 2014Of the deaths attributed to cancer, 90% are due to metastasis, and treatments that prevent or cure metastasis remain elusive. Emerging data indicate that hypoxia and the... (Review)
Review
Of the deaths attributed to cancer, 90% are due to metastasis, and treatments that prevent or cure metastasis remain elusive. Emerging data indicate that hypoxia and the extracellular matrix (ECM) might have crucial roles in metastasis. During tumour evolution, changes in the composition and the overall content of the ECM reflect both its biophysical and biological properties and these strongly influence tumour and stromal cell properties, such as proliferation and motility. Originally thought of as independent contributors to metastatic spread, recent studies have established a direct link between hypoxia and the composition and the organization of the ECM, which suggests a new model in which multiple microenvironmental signals might converge to synergistically influence metastatic outcome.
Topics: Extracellular Matrix; Humans; Hypoxia; Neoplasm Metastasis; Neoplasms
PubMed: 24827502
DOI: 10.1038/nrc3726 -
International Journal of Molecular... Oct 2022Intermittent hypoxia (IH), one of the primary pathologies of sleep apnea syndrome (SAS), exposes cells throughout the body to repeated cycles of hypoxia/normoxia that... (Review)
Review
Intermittent hypoxia (IH), one of the primary pathologies of sleep apnea syndrome (SAS), exposes cells throughout the body to repeated cycles of hypoxia/normoxia that result in oxidative stress and systemic inflammation. Since SAS is epidemiologically strongly correlated with type 2 diabetes/insulin resistance, obesity, hypertension, and dyslipidemia included in metabolic syndrome, the effects of IH on gene expression in the corresponding cells of each organ have been studied intensively to clarify the molecular mechanism of the association between SAS and metabolic syndrome. Dementia has recently been recognized as a serious health problem due to its increasing incidence, and a large body of evidence has shown its strong correlation with SAS and metabolic disorders. In this narrative review, we first outline the effects of IH on the expression of genes related to metabolism in neuronal cells, pancreatic β cells, hepatocytes, adipocytes, myocytes, and renal cells (mainly based on the results of our experiments). Next, we discuss the literature regarding the mechanisms by which metabolic disorders and IH develop dementia to understand how IH directly and indirectly leads to the development of dementia.
Topics: Humans; Diabetes Mellitus, Type 2; Metabolic Syndrome; Hypoxia; Cognition; Dementia
PubMed: 36361741
DOI: 10.3390/ijms232112957 -
Respiratory Care Oct 2014Oxygen is essential for normal aerobic metabolism in mammals. Hypoxia is the presence of lower than normal oxygen content and pressure in the cell. Causes of hypoxia... (Review)
Review
Oxygen is essential for normal aerobic metabolism in mammals. Hypoxia is the presence of lower than normal oxygen content and pressure in the cell. Causes of hypoxia include hypoxemia (low blood oxygen content and pressure), impaired oxygen delivery, and impaired cellular oxygen uptake/utilization. Many compensatory mechanisms exist at the global, regional, and cellular levels to allow cells to function in a hypoxic environment. Clinical management of tissue hypoxia usually focuses on global hypoxemia and oxygen delivery. As we move into the future, the clinical focus needs to change to assessing and managing mission-critical regional hypoxia to avoid unnecessary and potential toxic global strategies. We also need to focus on understanding and better harnessing the body's own adaptive mechanisms to hypoxia.
Topics: Adaptation, Physiological; Humans; Hypoxia; Oxygen; Oxygen Inhalation Therapy
PubMed: 25161296
DOI: 10.4187/respcare.03357 -
Respiratory Care Jun 2019For more than 40 years, noninvasive ventilation has been the first-line preferred therapy for acute-on-chronic conditions, such as COPD and cardiogenic pulmonary edema.... (Review)
Review
For more than 40 years, noninvasive ventilation has been the first-line preferred therapy for acute-on-chronic conditions, such as COPD and cardiogenic pulmonary edema. The use of noninvasive ventilation in the treatment of hypoxemic respiratory failure, however, has been met with mixed results associated with higher risks of intubation (failure of therapy) and with higher risks of mortality. The purpose of this review was to describe the current evidence and important considerations when patients with hypoxemic respiratory failure are managed with noninvasive ventilation.
Topics: Acute Disease; Humans; Hypoxia; Noninvasive Ventilation; Patient Selection; Practice Guidelines as Topic; Respiratory Insufficiency; Risk Factors; Severity of Illness Index
PubMed: 31110033
DOI: 10.4187/respcare.06735 -
Respiratory Care Jul 2021Hypoxemia is common in postoperative patients and is associated with prolonged hospital stays, high costs, and increased mortality. This review discusses the... (Review)
Review
Hypoxemia is common in postoperative patients and is associated with prolonged hospital stays, high costs, and increased mortality. This review discusses the postoperative management of hypoxemia in regard to the use of conventional oxygen therapy, high-flow nasal cannula oxygen therapy, CPAP, and noninvasive ventilation. The recommendations made are based on the currently available evidence.
Topics: Cannula; Continuous Positive Airway Pressure; Humans; Hypoxia; Noninvasive Ventilation; Oxygen; Oxygen Inhalation Therapy
PubMed: 34006596
DOI: 10.4187/respcare.08929 -
American Journal of Physiology.... Nov 2014Intermittent hypoxia (IH) has been the subject of considerable research in recent years, and triggers a bewildering array of both detrimental and beneficial effects in... (Review)
Review
Intermittent hypoxia (IH) has been the subject of considerable research in recent years, and triggers a bewildering array of both detrimental and beneficial effects in multiple physiological systems. Here, we review the extensive literature concerning IH and its impact on the respiratory, cardiovascular, immune, metabolic, bone, and nervous systems. One major goal is to define relevant IH characteristics leading to safe, protective, and/or therapeutic effects vs. pathogenesis. To understand the impact of IH, it is essential to define critical characteristics of the IH protocol under investigation, including potentially the severity of hypoxia within episodes, the duration of hypoxic episodes, the number of hypoxic episodes per day, the pattern of presentation across time (e.g., within vs. consecutive vs. alternating days), and the cumulative time of exposure. Not surprisingly, severe/chronic IH protocols tend to be pathogenic, whereas any beneficial effects are more likely to arise from modest/acute IH exposures. Features of the IH protocol most highly associated with beneficial vs. pathogenic outcomes include the level of hypoxemia within episodes and the number of episodes per day. Modest hypoxia (9-16% inspired O2) and low cycle numbers (3-15 episodes per day) most often lead to beneficial effects without pathology, whereas severe hypoxia (2-8% inspired O2) and more episodes per day (48-2,400 episodes/day) elicit progressively greater pathology. Accumulating evidence suggests that "low dose" IH (modest hypoxia, few episodes) may be a simple, safe, and effective treatment with considerable therapeutic potential for multiple clinical disorders.
Topics: Animals; Bone and Bones; Cardiovascular System; Humans; Hypoxia; Inflammation; Nervous System; Oxygen; Respiratory System; Time Factors
PubMed: 25231353
DOI: 10.1152/ajpregu.00208.2014 -
Kardiologia Polska Jun 2019High altitude is a fascinating model of hypoxia effects on the human body but is also an extreme environment which directly influences millions of people who either... (Review)
Review
High altitude is a fascinating model of hypoxia effects on the human body but is also an extreme environment which directly influences millions of people who either travel to high altitude locations or live there permanently. A significant progress was made over the past decades in the understanding of physiological background of responses to altitude, and recently a number of studies regarding clinical aspects of high altitude exposure were published. In particular, more is known about the changes occurring in systemic blood pressure in individuals exposed to high altitude as well as on the effects of antihypertensive drugs in this setting. The present article provides an overview of principal physiological and clinical aspects related to systemic blood pressure control and its changes at high altitude, mainly during the acute exposure. The evidence on blood pressure changes at rest and during exercise is discussed, as well as the underlying mechanisms and possible clinical implications.
Topics: Altitude; Altitude Sickness; Antihypertensive Agents; Atmospheric Pressure; Blood Pressure; Humans; Hypertension; Hypoxia
PubMed: 31099758
DOI: 10.33963/KP.14832 -
Birth Defects Research Oct 2017Hemochorial placentation is orchestrated through highly regulated temporal and spatial decisions governing the fate of trophoblast stem/progenitor cells. Trophoblast... (Review)
Review
Hemochorial placentation is orchestrated through highly regulated temporal and spatial decisions governing the fate of trophoblast stem/progenitor cells. Trophoblast cell acquisition of specializations facilitating invasion and uterine spiral artery remodeling is a labile process, sensitive to the environment, and represents a process that is vulnerable to dysmorphogenesis in pathologic states. Hypoxia is a signal guiding placental development, and molecular mechanisms directing cellular adaptations to low oxygen tension are integral to trophoblast cell differentiation and placentation. Hypoxia can also be used as an experimental tool to investigate regulatory processes controlling hemochorial placentation. These developmental processes are conserved in mouse, rat, and human placentation. Consequently, elements of these developmental events can be modeled and hypotheses tested in trophoblast stem cells and in genetically manipulated rodents. Hypoxia is also a consequence of a failed placenta, yielding pathologies that can adversely affect maternal adjustments to pregnancy, fetal health, and susceptibility to adult disease. The capacity of the placenta for adaptation to environmental challenges highlights the importance of its plasticity in safeguarding a healthy pregnancy. Birth Defects Research 109:1309-1329, 2017.© 2017 Wiley Periodicals, Inc.
Topics: Adaptation, Physiological; Animals; Female; Humans; Hypoxia; Maternal-Fetal Exchange; Oxygen; Placentation; Pregnancy; Signal Transduction
PubMed: 29105383
DOI: 10.1002/bdr2.1135