Diurnal differences in cerebral microvascular blood flow and oxygen delivery across brain regions in awake mice.

Significance: Elucidating the diurnal differences in cerebral hemodynamics is essential for both advancing our understanding of brain function and improving therapeutic strategies for neurological disorders. However, it remains unclear how the inactive and active diurnal phases influence the microvascular-scale distributions of cerebral blood flow and oxygenation and whether these distributions exhibit brain-region-specific variations. Aim: We aim to characterize the time-of-day variations in cerebral microvascular blood flow and oxygenation across brain regions in awake mice. Approach: We used two-photon microscopy and Doppler optical coherence tomography to quantify the resting-state microvascular blood flow and oxygenation parameters in the cerebral middle-cerebral-artery (MCA) territory and adjacent watershed area in the head-restrained, awake mice, during the inactive and active phases. Results: Microvascular blood flow was consistently higher during the inactive phase compared with the active phase. Specifically, this elevated flow reached statistical significance in the watershed area. Furthermore, oxygen extraction fraction increased in the MCA territory during the active phase but decreased in the watershed area. Conclusions: We reveal diurnal differences in cerebral microvascular blood flow and oxygenation, with the watershed area exhibiting a greater response to this effect. These findings underscore the potential of chronotherapeutic strategies to enhance treatment efficacy for cerebrovascular disorders.