Sex shapes capillary flows and oxygen extraction in the middle-aged mouse brain

Sex influences cerebral blood circulation and oxygen utilization in middle-aged mice, according to a recent study. At 15 months of age, female mice exhibit higher cortical blood flow compared to male counterparts, despite converging pulsatility and resistance differences, and comparable estrogen levels. Utilizing indicator-dilution and intravascular oxygen measurements via two-photon microscopy, researchers discovered that capillary transit-time variability (CTH) escalates more rapidly with mean transit time in females, suggesting a passively regulated capillary network.

This finding is coupled with diminished oxygen extraction fraction (OEF) without arterial oxygen delivery impairment. Spatial transcriptomics data indicate that sex disparities are regionally specific, particularly in white matter, where a male-associated myelin and axonogenesis signature coexists with smaller white matter volumes in females.

These molecular and structural distinctions align with heightened hippocampal microglial activity and altered spatial search patterns in females, all while maintaining normal circulating stress markers, blood-brain barrier integrity, and immunity levels. In summary, these results suggest that sex differences in aging brains manifest at the capillary flow regulation and regional tissue program level rather than through overall cerebral blood flow, and that increased blood flow in females may conceal, rather than signify, sufficient tissue oxygenation.