EXPRESS: Persistent cerebrovascular dysfunction and altered mural cell calcium signaling after sepsis recovery in female mice

Background: Sepsis is associated with long-term cognitive impairment, yet the cerebrovascular mechanisms underlying these deficits remain poorly understood, particularly after clinical recovery. Although cerebral blood flow abnormalities are well documented during acute sepsis, whether microvascular dysfunction persists and how mural cells contribute to these changes remain unknown. Methods: We used longitudinal in vivo two-photon imaging in a fecal-induced peritonitis model to examine pericyte calcium signaling, microvascular hemodynamics, vasomotion, and neurovascular coupling before and after sepsis in the same female mice. Results: Two weeks after sepsis, when mice no longer exhibited clinical signs of illness, both ensheathing and thin-strand pericytes displayed persistently elevated basal Ca 2 ⁺ activity. In the arteriole–capillary transition zone, elevated ensheathing pericyte Ca 2 ⁺ was paradoxically associated with vessel dilation and diminished vasomotor activity. These abnormalities were accompanied by altered red blood cell distribution and attenuated vascular responses during neurovascular coupling. Conclusion: Together, these findings demonstrate that clinically recovered mice exhibit persistent abnormalities in pericyte calcium signaling, microvascular blood flow regulation, and neurovascular coupling-associated vascular responses, identifying pericyte dysfunction as a potential contributor to long-term cerebrovascular impairment after sepsis.