Spatiotemporal dynamics of brain pericytes in ischemic stroke

Pericytes constitute a vital component of the neurovascular unit (NVU) and play a pivotal role in the pathophysiology of ischemic stroke (IS). They perform a variety of critical functions, involving regulating cerebral blood flow (CBF), modulating inflammatory responses, exhibiting stem cell-like properties, and maintaining the integrity of the blood-brain barrier (BBB). During the hyperacute and acute phases of IS, pericytes undergo contraction, contributing to the no-reflow phenomenon (NRP) and compromising BBB integrity. Concurrently, their activation exacerbates neuroinflammation and secondary injury. In contrast, the subacute and chronic phases are characterized by pericyte-mediated reparative processes, including angiogenesis, vascular stabilization, immune modulation, and scar formation. Notably, distinct pericyte subpopulations residing within specific vascular segments, pre-capillary, capillary, and post-capillary, demonstrate unique spatial and temporal functional patterns within the infarct core, penumbra, and peri-infarct regions. By examining these multifaceted dynamics, this review also highlights the intricate characteristics of pericytes as a therapeutic target and investigates novel therapeutic approaches based on their spatiotemporal functional modulation, with the goals of improving microcirculatory disorders, protecting the BBB, decreasing inflammation, and promoting neural repairs.