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Intermittent Hypoxia: Physiological and Biomedical Perspectives

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 April 2026 | Viewed by 418

Special Issue Editors


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Guest Editor

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Guest Editor
1. Translational Research Group on Cardiovascular Respiratory Diseases (CAREs), Dr. Josep Trueta University Hospital de Girona, Santa Caterina Hospital de Salt and the Girona Biomedical Research Institute (IDIBGI-CERCA), 17190 Girona, Spain
2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
3. Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Villarroel, 170, 08036 Barcelona, Spain
4. Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), 28029 Madrid, Spain
Interests: angiogenesis; hypoxia; endothelial dysfunction; pulmonary hypertension; sleep apnea
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Guest Editor
Department of Cell Biology, Physiology and Immunology. Universitat de Barcelona. 08028 Barcelona, Catalonia, Spain
Interests: oxidants and antioxidants in physiology; intermittent hypoxia and neuroprotection in postischemic processes; molecular mechanisms induced by hypothermia in isolated rat liver

Special Issue Information

Dear Colleagues,

Intermittent hypoxia (IH) refers to repeated episodes of reduced oxygen availability, alternating with periods of normoxia. This phenomenon can occur naturally, such as during altitude training, or pathologically, as in respiratory disorders like obstructive sleep apnea. In recent decades, intermittent hypoxia has become a relevant field of study in both physiology and pathophysiology due to its ability to induce cellular and systemic adaptations that may be beneficial or, conversely, contribute to disease progression when dysregulated.

The molecular mechanisms involved in the response to hypoxia include activation of hypoxia-inducible factors (HIFs), oxidative stress, inflammation, and vascular remodeling.

In sports, IH has been used as a strategy to enhance aerobic performance and physiological adaptability. Hypoxic training has been shown to achieve the following:

  • Elevate erythropoietin (EPO) levels, enhancing erythropoiesis and oxygen transport;
  • Improve mitochondrial efficiency and muscular oxidative capacity;
  • Promote vasodilation and tissue perfusion via nitric oxide pathways;
  • Increase tolerance to metabolic stress, supporting endurance in high-intensity disciplines.

Such adaptations are particularly advantageous in endurance-based sports such as cycling, long-distance running, and team-based athletics.

Beyond its applications in sports, IH has emerged as a promising therapeutic modality with notable clinical relevance. When employed as a preconditioning strategy prior to ischemia–reperfusion events—commonly encountered during cardiac surgery and organ transplantation—IH preconditioning has demonstrated the ability to foster tissue and organ resistance or tolerance to subsequent injury.

However, IH can also have adverse effects, especially in the context of chronic respiratory diseases. In individuals with conditions like sleep apnea, chronic obstructive pulmonary disease (COPD), or pulmonary fibrosis, IH has been implicated in the following:

  • Sustained oxidative stress and systemic inflammation;
  • Impaired cardiovascular regulation, elevating the risk of hypertension and cardiac dysfunction;
  • Neurocognitive decline due to recurrent cerebral hypoxia;
  • Pathological vascular remodeling, contributing to pulmonary hypertension.

These negative effects highlight the importance of understanding the differential mechanisms of intermittent hypoxia, whether it occurs in a physiological or pathological context.

We are pleased to announce a forthcoming Special Issue dedicated to the exploration of intermittent hypoxia from both physiological and biomedical perspectives. We invite researchers and clinicians to submit high-quality contributions that advance our understanding of this multifaceted phenomenon.

We welcome original research articles and comprehensive reviews addressing (but not limited to) the following:

  • Mechanisms of adaptation to intermittent hypoxia;
  • Applications in sports science and performance enhancement;
  • Pathophysiological effects in chronic respiratory and cardiovascular diseases;
  • Therapeutic strategies and clinical implications of IH exposure.

This Special Issue offers a unique platform to showcase cutting-edge research and foster interdisciplinary dialogue. We seek contributions that will shape the future of IH research and its applications in health and disease and look forward to hearing from you. This Special Issue is coordinated with the assistance of Dr. Marcelo Tuesta (Faculty of Rehabilitation Sciences, Andres Bello University, Chile).

Dr. Teresa Carbonell Camós
Dr. Olga Tura-Ceide
Dr. Norma Alva
Guest Editors

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Keywords

  • altitude training
  • cardiovascular adaptation
  • endothelial dysfunction
  • EPO
  • intermittent hypoxia conditioning programs
  • HIF-1
  • neuroplasticity
  • obstructive sleep apnea
  • oxidative stress
  • pulmonary hypertension

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Published Papers (1 paper)

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19 pages, 5470 KB  
Article
Neuroplastic Effects Induced by Hypercapnic Hypoxia in Rat Focal Ischemic Stroke Are Driven via BDNF and VEGF Signaling
by Pavel P. Tregub, Pavel A. Chekulaev, Georgy M. Zembatov, Eugenia D. Namiot, Michael A. Ignatyuk, Dmitrii A. Atiakshin, Arseniy K. Berdnikov, Zaripat Sh. Manasova, Peter F. Litvitskiy and Vladimir P. Kulikov
Int. J. Mol. Sci. 2025, 26(24), 12019; https://doi.org/10.3390/ijms262412019 - 13 Dec 2025
Viewed by 259
Abstract
In this study, the neurorehabilitation potential of combined and isolated intermittent hypercapnia and hypoxia exposure was evaluated following photochemically induced cerebral thrombosis in rats. Particular attention was given to the roles of possible neuroplasticity mechanisms mediated by VEGF and BDNF, as well as [...] Read more.
In this study, the neurorehabilitation potential of combined and isolated intermittent hypercapnia and hypoxia exposure was evaluated following photochemically induced cerebral thrombosis in rats. Particular attention was given to the roles of possible neuroplasticity mechanisms mediated by VEGF and BDNF, as well as the potential of hypercapnic–hypoxic interventions to synergistically amplify the therapeutic effects of pharmacological neuroprotectants during recovery. A total of 50 male Wistar rats were randomly assigned to five equal groups (n = 10 per group), each undergoing a course of respiratory interventions lasting 30 min per day for 15 sessions. The groups included (1) a normobaric hypoxia (PO2 ≈ 90 mmHg) group, (2) a permissive hypercapnia (PCO2 ≈ 50 mmHg) group, (3) a combined hypercapnic hypoxia (PO2 ≈ 90 mmHg, PCO2 ≈ 50 mmHg) group, (4) a control group, and (5) a sham-operated group. Following the rehabilitation protocol, animals exposed to hypercapnic hypoxia exhibited a two-fold reduction in stroke volume compared with controls, significant improvement in motor coordination (as assessed via the rotarod test), and marked upregulation of VEGF and BDNF expression within the ischemic brain region. Notably, only the HH group showed a decrease in serum neuron-specific enolase (NSE) levels. These findings indicate that hypercapnic hypoxia exerts a possible neurorehabilitative effect after focal ischemic injury, superior to that of isolated hypoxia or hypercapnia. Possible mechanisms underlying this outcome may involve activation of neurotrophic (BDNF) and angiogenic (VEGF) signaling pathways. Full article
(This article belongs to the Special Issue Intermittent Hypoxia: Physiological and Biomedical Perspectives)
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