Date of Completion
2025
Document Type
Honors College Thesis
Department
Neuroscience
Thesis Type
Honors College, College of Arts and Science Honors
First Advisor
Dr. Nicholas Klug
Second Advisor
Dr. Molly Stanley
Third Advisor
Dr. Yangguang Ou
Keywords
hypoxia, cerebral blood flow, adenosine, penetrating arterioles, pial arteries, capillaries
Abstract
The brain, a major consumer of oxygen and nutrients, is perfused by an extensive vascular network that tightly regulates cerebral blood flow (CBF). Episodes of hypoxia are rapidly corrected in healthy conditions by CBF increase, with failure to do so contributing to pathology like cerebral small vessel disease (cSVD). The mechanisms linking hypoxia to vascular responses, and their breakdown in disease, is unclear. Hypoxia substantially elevates brain adenosine levels, which has a well-documented dilatory effect on large surface brain vessels. However, most of the brain vasculature is made up of small parenchymal arterioles and capillaries (> 95%), where the effects of hypoxia and adenosine are unknown. This project investigated the mechanisms of hypoxia-induced vasodilation and adenosine signaling in the cerebral vasculature. Dilation of isolated pial arteries to adenosine was investigated in the presence of U46619, a thromboxane A2 (TXA2) receptor agonist, and paxilline, a large conductance voltage- and Ca2+-activated K+ channel (BKCa) blocker, with no notable dilation under either condition. The response to hypoxia in pial vessels and penetrating arterioles was characterized using two-photon microscopy, with the penetrating arterioles demonstrating a significantly greater dilation to hypoxia. The presence of adenosine A2A receptor antagonist ZM 241385 modestly impaired hypoxia-induced dilation. These findings suggest that hypoxia-induced adenosine signaling differs between vascular zones, with penetrating arterioles displaying greater sensitivity than pial arteries, and that BKCa channels may not be a downstream target of physiological adenosine signaling. This work offers important insight into CBF regulation and lays groundwork for future investigations of the microvasculature.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Recommended Citation
Hand, Lillian Sarah, "The Role of Cerebral Adenosine Sensing Across the Artery-Capillary Continuum" (2025). UVM Patrick Leahy Honors College Senior Theses. 719.
https://scholarworks.uvm.edu/hcoltheses/719