Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions
Open accessAbstract
Oxygen transport imposes a possible constraint on the brain's ability to sustain variable metabolic demands, but oxygen diffusion in the cerebral cortex has not yet been observed directly. We show that concurrent two-photon fluorescence imaging of endogenous nicotinamide adenine dinucleotide (NADH) and the cortical microcirculation exposes well-defined boundaries of tissue oxygen diffusion in the mouse cortex. The NADH fluorescence increases rapidly over a narrow, very low pO 2 range with a p 50 of 3.4±0.6 mm Hg, thereby establishing a nearly binary reporter of significant, metabolically limiting hypoxia. The transient cortical tissue boundaries of NADH fluorescence exhibit remarkably delineated geometrical patterns, which define the limits of tissue oxygen diffusion from the cortical microcirculation and bear a striking resemblance to the ideal Krogh tissue cylinder. The visualization of microvessels and their regional contribution to oxygen delivery establishes penetrating arterioles as major oxygen sources in addition to the capillary network and confirms the existence of cortical oxygen fields with steep microregional oxygen gradients. Thus, two-photon NADH imaging can be applied to expose vascular supply regions and to localize functionally relevant microregional cortical hypoxia with micrometer spatial resolution.
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In the photothrombotic model, dendritic structure could be maintained in the ischaemic tissue in the presence of a flowing capillary ~80 mm away, and arterioles can supply oxygen even over longer distances, well above 100 mm.
“In the photothrombotic model, dendritic structure could be maintained in the ischaemic tissue in the presence of a flowing capillary $80 mm away (Zhang and Murphy, 2007), and arterioles can supply oxygen even over longer distances, well above 100 mm (Kasischke et al., 2011).”
From Evolution of neuronal and astroglial disruption in the peri-contusional cortex of mice revealed by in vivo two-photon imaging (2013) · cites this paper as Kasischke et al., 2011
The Results section (page unavailable) identifies penetrating arterioles as oxygen sources, but reports radial diffusion distances of >50 μm, not well above 100 μm. The Discussion (page unavailable) says the oxygen-supplied tissue cylinders have diameters well above 100 μm; the citing sentence appears to mistake that diameter for the distance oxygen travels from an arteriole. The photothrombotic-model clause is attributed to a different source. (LLM, conf=0.89)
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References 51 · Cited by 160
- Authors
- Kasischke, K. A., Lambert, E. M., Panepento, B., Sun, A., Gelbard, H. A., Burgess, R. W., Foster, T. H., & Nedergaard, M.
- Affiliations
- University of Rochester Medicine (US)
- Jackson Laboratory (US)
- Corresponding author
- Kasischke, Karl A
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2010-09-22
- Volume
- 31
- Issue
- 1
- Pages
- 68-81
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC3049466
- OpenAlex
- W2065283157
- Semantic Scholar
- 004adda1421715429972b9d58be2343f2bee26fd
- Cited by
- 160
- References
- 51
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 12 · 2023: 7 · 2022: 7 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 10 · 2017: 17 · 2016: 13 · 2015: 20 · 2014: 11 · 2013: 14 · 2012: 14
- FWCI
- 10.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Cancer Institute (R01CA068409, CA68409)
- National Institute of Neurological Disorders and Stroke (NS38073, R01NS038073, NS50315, P01NS050315)
- 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
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- oxygen diffusion, cerebral cortex, cortical microcirculation, hypoxia, oxygen gradients, penetrating arterioles, capillary network, cerebral blood flow, mouse cortex
- MeSH terms
- Algorithms, Animals, Cerebral Angiography, Hypoxia, Brain, Cerebral Cortex, Cerebrovascular Circulation, Diffusion, Image Processing, Computer-Assisted, Mice, Inbred C57BL, Microcirculation, NAD, Oxygen Consumption, Physical Stimulation, Pia Mater, Somatosensory Cortex, Spectrometry, Fluorescence, Vibrissae, Absorptiometry, Photon, Cell Hypoxia, Mice, Electrophysiological Phenomena
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