Cortical Microvascular Pulsatility in the Aging Mouse Brain and the Confounding Effects of Anesthesia

Abnormal cerebrovascular pulsatility is associated with white-matter injury, blood-brain-barrier leakage, and impaired glymphatic clearance, yet its extent in the microvasculature and aging dynamics remained obscured due to experimental and technical limitations. A multi-modal approach for quantifying flow and diameter pulsatility in small cerebral vessels is developed and applied it longitudinally in male C57BL/6JRj mice from 18 to 81 weeks, both in awake and anesthetized conditions. In the awake state, mean perfusion and pulsatility indexes varied by <10%, indicating preserved hemodynamics until late life when arterial diameter pulsatility and venular caliber rose modestly. Anaesthesia radically changes the microvascular dynamics: isoflurane produces age-dependent hyperemia, and both isoflurane and ketamine-xylazine double flow pulsatility and reshape diameter oscillations in drug-specific ways. To complement the longitudinal data from males, a separate cross-sectional comparison between sexes at 50-51 weeks of age is performed, which reveal significantly lower microvascular flow pulsatility in females despite no difference in mean perfusion. The results suggest that microvascular pulsatility remains stable during healthy aging yet can shift dramatically depending on the animal's condition, even if average cerebral perfusion is unchanged.