Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia
The review introduces the stages of formation and experimental confirmation of the hypothesis regarding the mutual potentiation of neuroprotective effects of hypoxia and hypercapnia during their combined influence (hypercapnic hypoxia). The main focus is on the mechanisms and signaling pathways invo...
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/3665 |
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| author | Pavel P. Tregub Vladimir P. Kulikov Irada Ibrahimli Oksana F. Tregub Artem V. Volodkin Michael A. Ignatyuk Andrey A. Kostin Dmitrii A. Atiakshin |
| author_facet | Pavel P. Tregub Vladimir P. Kulikov Irada Ibrahimli Oksana F. Tregub Artem V. Volodkin Michael A. Ignatyuk Andrey A. Kostin Dmitrii A. Atiakshin |
| author_sort | Pavel P. Tregub |
| collection | DOAJ |
| description | The review introduces the stages of formation and experimental confirmation of the hypothesis regarding the mutual potentiation of neuroprotective effects of hypoxia and hypercapnia during their combined influence (hypercapnic hypoxia). The main focus is on the mechanisms and signaling pathways involved in the formation of ischemic tolerance in the brain during intermittent hypercapnic hypoxia. Importantly, the combined effect of hypoxia and hypercapnia exerts a more pronounced neuroprotective effect compared to their separate application. Some signaling systems are associated with the predominance of the hypoxic stimulus (HIF-1α, A1 receptors), while others (NF-κB, antioxidant activity, inhibition of apoptosis, maintenance of selective blood–brain barrier permeability) are mainly modulated by hypercapnia. Most of the molecular and cellular mechanisms involved in the formation of brain tolerance to ischemia are due to the contribution of both excess carbon dioxide and oxygen deficiency (ATP-dependent potassium channels, chaperones, endoplasmic reticulum stress, mitochondrial metabolism reprogramming). Overall, experimental studies indicate the dominance of hypercapnia in the neuroprotective effect of its combined action with hypoxia. Recent clinical studies have demonstrated the effectiveness of hypercapnic–hypoxic training in the treatment of childhood cerebral palsy and diabetic polyneuropathy in children. Combining hypercapnic hypoxia with pharmacological modulators of neuro/cardio/cytoprotection signaling pathways is likely to be promising for translating experimental research into clinical medicine. |
| first_indexed | 2024-04-24T10:43:56Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:43:56Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f48389ad15ba473daa2f32bf749cc4712024-04-12T13:19:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01257366510.3390/ijms25073665Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic HypoxiaPavel P. Tregub0Vladimir P. Kulikov1Irada Ibrahimli2Oksana F. Tregub3Artem V. Volodkin4Michael A. Ignatyuk5Andrey A. Kostin6Dmitrii A. Atiakshin7Department of Pathophysiology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, RussiaDepartment of Ultrasound and Functional Diagnostics, Altay State Medical University, 656040 Barnaul, RussiaDepartment of Pathophysiology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, RussiaIndependent Researcher, 127055 Moscow, RussiaScientific and Educational Resource Center “Innovative Technologies of Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis”, RUDN University, 117198 Moscow, RussiaScientific and Educational Resource Center “Innovative Technologies of Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis”, RUDN University, 117198 Moscow, RussiaScientific and Educational Resource Center “Innovative Technologies of Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis”, RUDN University, 117198 Moscow, RussiaScientific and Educational Resource Center “Innovative Technologies of Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis”, RUDN University, 117198 Moscow, RussiaThe review introduces the stages of formation and experimental confirmation of the hypothesis regarding the mutual potentiation of neuroprotective effects of hypoxia and hypercapnia during their combined influence (hypercapnic hypoxia). The main focus is on the mechanisms and signaling pathways involved in the formation of ischemic tolerance in the brain during intermittent hypercapnic hypoxia. Importantly, the combined effect of hypoxia and hypercapnia exerts a more pronounced neuroprotective effect compared to their separate application. Some signaling systems are associated with the predominance of the hypoxic stimulus (HIF-1α, A1 receptors), while others (NF-κB, antioxidant activity, inhibition of apoptosis, maintenance of selective blood–brain barrier permeability) are mainly modulated by hypercapnia. Most of the molecular and cellular mechanisms involved in the formation of brain tolerance to ischemia are due to the contribution of both excess carbon dioxide and oxygen deficiency (ATP-dependent potassium channels, chaperones, endoplasmic reticulum stress, mitochondrial metabolism reprogramming). Overall, experimental studies indicate the dominance of hypercapnia in the neuroprotective effect of its combined action with hypoxia. Recent clinical studies have demonstrated the effectiveness of hypercapnic–hypoxic training in the treatment of childhood cerebral palsy and diabetic polyneuropathy in children. Combining hypercapnic hypoxia with pharmacological modulators of neuro/cardio/cytoprotection signaling pathways is likely to be promising for translating experimental research into clinical medicine.https://www.mdpi.com/1422-0067/25/7/3665hypoxiahypercapnianeuroprotectionblood–brain barrier permeabilityapoptosis inhibitionantioxidant systems |
| spellingShingle | Pavel P. Tregub Vladimir P. Kulikov Irada Ibrahimli Oksana F. Tregub Artem V. Volodkin Michael A. Ignatyuk Andrey A. Kostin Dmitrii A. Atiakshin Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia International Journal of Molecular Sciences hypoxia hypercapnia neuroprotection blood–brain barrier permeability apoptosis inhibition antioxidant systems |
| title | Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia |
| title_full | Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia |
| title_fullStr | Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia |
| title_full_unstemmed | Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia |
| title_short | Molecular Mechanisms of Neuroprotection after the Intermittent Exposures of Hypercapnic Hypoxia |
| title_sort | molecular mechanisms of neuroprotection after the intermittent exposures of hypercapnic hypoxia |
| topic | hypoxia hypercapnia neuroprotection blood–brain barrier permeability apoptosis inhibition antioxidant systems |
| url | https://www.mdpi.com/1422-0067/25/7/3665 |
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