Microglial cyclooxygenase-1 modulates cerebral capillary basal tone in vivo in mice

William A. Mills (), Niesha A. Savory, Aida Oryza Lopez-Ortiz, Dennis H. Lentferink, Fernando González Ibáñez, Praise Agochi, Elina Rastegar, Arnav Gupta, Deetya Gupta, Arya Suram, Brant E. Isakson, Marie-Ève Tremblay and Ukpong B. Eyo ()
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William A. Mills: University of Virginia School of Medicine
Niesha A. Savory: University of Virginia School of Medicine
Aida Oryza Lopez-Ortiz: University of Virginia School of Medicine
Dennis H. Lentferink: University of Virginia School of Medicine
Fernando González Ibáñez: Centre de recherche du CHU de Québec-Université Laval
Praise Agochi: University of Virginia School of Medicine
Elina Rastegar: University of Virginia School of Medicine
Arnav Gupta: University of Virginia School of Medicine
Deetya Gupta: University of Virginia School of Medicine
Arya Suram: University of Virginia School of Medicine
Brant E. Isakson: University of Virginia School of Medicine
Marie-Ève Tremblay: Centre de recherche du CHU de Québec-Université Laval
Ukpong B. Eyo: University of Virginia School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: Abstract Microglia and border associated macrophages have been implicated in hypercapnia, but it is unknown which myeloid cell modulates which vessel type. Previously, we documented in mice myeloid cell association with the brain vasculature but did not distinguish their localization along the vascular tree. Using molecular approaches to distinguish microglia and perivascular macrophages, we show that microglia are the only myeloid cells associating with capillaries. To determine if loss of microglia is sufficient to reduce capillary tone, we employ global and focal ablations and find significant reductions in capillary diameter and red blood cell flux, suggesting vasodilatory regulation by microglia. Cyclooxygenase-1 (COX1), an enzyme with known vasodilatory action, is predominantly expressed by microglia. To determine the necessity of microglial COX1 in regulating cerebral basal capillary tone in vivo, we perform genetic ablation and find a significant reduction in capillary flux and diameter. Together, this study using male mouse models reveals a role for microglial COX1 in maintaining basal capillary tone in vivo.

Date: 2025
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DOI: 10.1038/s41467-025-60753-x

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