Oxygen imaging of hypoxic pockets in the mouse cerebral cortex
Open accessAbstract
Consciousness is lost within seconds upon cessation of cerebral blood flow. The brain cannot store oxygen, and interruption of oxidative phosphorylation is fatal within minutes. Yet only rudimentary knowledge exists regarding cortical partial oxygen tension ( P o 2 ) dynamics under physiological conditions. Here we introduce Green enhanced Nano-lantern (GeNL), a genetically encoded bioluminescent oxygen indicator for P o 2 imaging. In awake behaving mice, we uncover the existence of spontaneous, spatially defined “hypoxic pockets” and demonstrate their linkage to the abrogation of local capillary flow. Exercise reduced the burden of hypoxic pockets by 52% compared with rest. The study provides insight into cortical oxygen dynamics in awake behaving animals and concurrently establishes a tool to delineate the importance of oxygen tension in physiological processes and neurological diseases.
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Cortical tissue can intermittently become locally hypoxic even under healthy conditions.
“Previous studies have shown that cortical tissue can intermittently become locally hypoxic even under healthy conditions70, suggesting that such limitations of oxygen utilization may itself serve an adaptive function.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [70]
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- Authors
- Beinlich, F. R. M., Asiminas, A., Untiet, V., Bojarowska, Z., Plá, V., Sigurdsson, B., Timmel, V., Gehrig, L., Graber, M. H., Hirase, H., & Nedergaard, M.
- Affiliations
- University of Copenhagen (DK)
- Division of Glial Disease and Therapeutics, Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
- FHNW University of Applied Sciences and Arts Northwestern Switzerland (CH)
- Corresponding author
- Beinlich, Felix R. M.
- Nedergaard, Maiken
- ORCID
- Venue
- Science
- Published
- 2024-03-29
- Volume
- 383
- Issue
- 6690
- Pages
- 1471-1478
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC11251491
- OpenAlex
- W4393279563
- Cited by
- 82
- References
- 70
- Citations by year
- 2026: 22 · 2025: 42 · 2024: 18
- FWCI
- 20.89
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Funders
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Lundbeckfonden (R287‐2018‐2046)
- Novo Nordisk Fonden (NNF19OC0058058)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL122578)
- National Institute of Neurological Disorders and Stroke (U19NS128613)
- National Center for Complementary and Integrative Health (R01AT012312, R01AT011439)
- Army Research Office
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › bioluminescence and chemiluminescence research
- Keywords
- cerebral cortex, bioluminescence imaging, capillary flow, physical activity, awake behaving mice, neurovascular coupling
- MeSH terms
- Oxygen Saturation, Animals, Brain, Hypoxia, Brain, Cerebral Cortex, Cerebrovascular Circulation, Consciousness, Diagnostic Imaging, Hypercapnia, Luciferases, Luminescent Measurements, Oxygen, Partial Pressure, Recombinant Fusion Proteins, Vasodilation, Green Fluorescent Proteins, Mice
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