Mechanisms of neurovascular regulation in health and disease: Insights from experimental animal models

The brain is an energetically demanding organ that relies on a continuous and precisely regulated blood supply to sustain neuronal function. This regulation is achieved through an intricate vascular network and sophisticated control mechanisms that dynamically match cerebral blood flow (CBF) to local metabolic demands. Central to this process is the neurovascular unit (NVU), a multicellular ensemble composed of endothelial cells, mural cells, astrocytes, neurons, microglia, and extracellular matrix components. Through coordinated interactions, the NVU governs vascular tone, blood-brain barrier integrity, and metabolic exchange. In this Review, we first describe the structural organization of the cerebrovascular tree and the specialized features of its cellular constituents. We then examine the principal mechanisms controlling CBF, including neurovascular coupling, cerebrovascular autoregulation, and endothelial regulation of vascular tone, highlighting the underlying molecular and cellular pathways. Emphasis is placed on mechanistic insights derived from experimental animal models, which have been fundamental for dissecting the basic biology of neurovascular regulation. Finally, we discuss how disruption of these regulatory systems contributes to cerebrovascular and neurodegenerative diseases, including hypertension and Alzheimer's disease (AD), primarily drawing on preclinical evidence.