Microglial cyclooxygenase-1 modulates cerebral capillary basal tone in vivo

Myeloid cells, consisting of parenchymal-resident microglia and border associated macrophages (BAM), have been implicated in hypercapnia, but it is unknown which myeloid cell modulates which vessel type. In previous work, we documented that myeloid cells associate with the brain vasculature but did not distinguish their localization along the vascular tree. Here, using molecular approaches to distinguish microglia and perivascular macrophages, we establish that microglia are the only myeloid cells associating with capillaries which we refer to as capillary associated microglia (CAM). To determine if loss of CAM is sufficient to reduce capillary tone, we employed global and focal ablations and found 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 performed genetic ablation of microglial COX1 and found a significant reduction in capillary flux and diameter. Together, this study reveals a novel role for microglial COX1 in maintaining basal capillary tone in vivo that may be relevant for targeting in disease.