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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:p>Maintaining a stable cerebral blood flow (CBF) despite variations in blood pressure is crucial for normal brain function. This process, called cerebral autoregulation, is often impaired in pathologies such as ischemic stroke, underlining its clinical importance. However, how local vascular responses interact across complex cerebrovascular networks to stabilize perfusion remains poorly understood. Here, we present an in silico model of static autoregulation that can be applied to realistic microvascular networks, providing vessel-specific insights into vasoreactivity and perfusion dynamics. Our simulations revealed a hierarchical organization of autoregulatory responses, in which pial surface arteries act as key regulators that buffer pressure changes across large vascular territories. Arterial density emerged as a decisive determinant of network-specific autoregulatory capacity, highlighting the importance of vascular topology for maintaining stable perfusion. During poststroke reperfusion, alterations in vasoreactivity, rather than collateral extent alone, emerged as the main contributor to pathogenic hyperperfusion. Simulations of chronic autoregulatory dysfunction showed that progressive loss of vascular reactivity can produce substantial downstream disturbances in capillary perfusion and alter the autoregulation curve. Overall, our framework reveals how interactions between vascular topology and vessel-specific regulatory mechanisms shape CBF regulation across scales, from individual arteries to whole-network perfusion. 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