Journal Article

DZNE-2025-00047

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Effect of Acute Hypoxia Exposure on the Availability of A1 Adenosine Receptors and Perfusion in the Human Brain.

Michno, M. ; Schmitz, J. ; Foerges, A. L. ; Beer, S. ; Jordan, J. ; Neumaier, B. ; Drzezga, A.DZNE* ; Aeschbach, D. ; Bauer, A. ; Tank, J. ; Weis, H. ; Elmenhorst, E.-M. ; Elmenhorst, D.

2025
Soc. New York, NY

This record in other databases:  

Please use a persistent id in citations: doi:10.2967/jnumed.124.268455

Abstract: In animal studies it has been observed that the inhibitory neuromodulator adenosine is released into the cerebral interstitial space during hypoxic challenges. Adenosine's actions on the A1 adenosine receptor (A1AR) protect the brain from oxygen deprivation and overexertion through adjustments in cerebral blood flow, metabolism, and electric activity. Methods: Using 8-cyclopentyl-3-(3-[18F]fluoropropyl)-1-propylxanthine ([18F]CPFPX), a PET tracer for the A1AR, we tested the hypothesis that hypoxia-induced adenosine release reduces A1AR availability in the human brain. Furthermore, we investigated whether this response is associated with altered brain perfusion and psychomotor vigilance. Ten healthy volunteers completed a 110-min bolus-plus-constant-infusion [18F]CPFPX PET/MRI hybrid experiment including a 30-min interval of normobaric hypoxia with peripheral oxygen saturation between 70% and 75%. We obtained blood samples to calculate metabolite-corrected steady-state A1AR distribution volumes and measured gray matter brain perfusion via arterial spin labeling in high temporal resolution. A 3-min psychomotor vigilance test was conducted every 10 min, and heart rate and peripheral blood oxygen saturation were continuously measured. Results: In all 7 examined brain regions, hypoxia reduced A1AR availability significantly (e.g., frontal lobe, 13.5%; P = 0.0144) whereas gray matter brain perfusion increased (e.g., frontal lobe, 42.5%; P = 0.0007). Heart rate increased by 19% (P = 0.0039). Mean reaction speed decreased by 4.3% (P = 0.0021). Conclusion: Our study is the first, to our knowledge, to demonstrate that acute hypoxia, corresponding to a mean altitude of 5,500 m (18,000 ft), reduces A1AR availability in the human brain. The finding is consistent with hypoxia-induced cerebral adenosine release leading to increased A1AR occupancy.

Keyword(s): Humans (MeSH) ; Male (MeSH) ; Receptor, Adenosine A1: metabolism (MeSH) ; Adult (MeSH) ; Brain: diagnostic imaging (MeSH) ; Brain: metabolism (MeSH) ; Brain: blood supply (MeSH) ; Female (MeSH) ; Positron-Emission Tomography (MeSH) ; Cerebrovascular Circulation (MeSH) ; Hypoxia: metabolism (MeSH) ; Hypoxia: physiopathology (MeSH) ; Hypoxia: diagnostic imaging (MeSH) ; Young Adult (MeSH) ; Xanthines (MeSH) ; Magnetic Resonance Imaging (MeSH) ; A1AR ; ASL ; PET ; [18F]CPFPX ; adenosine receptors ; hypoxia ; Receptor, Adenosine A1 ; Xanthines ; 8-cyclopenta-3-(3-fluoropropyl)-1-propylxanthine

---

Contributing Institute(s):

1. Positron Emissions Tomography (PET) (AG Boecker)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---