Continued dysfunction of capillary pericytes promotes no-reflow after experimental stroke in vivo.

Incomplete reperfusion of the microvasculature ('no-reflow') after ischaemic stroke damages salvageable brain tissue. Previous ex vivo studies suggest pericytes are vulnerable to ischaemia and may exacerbate no-reflow, but the viability of pericytes and their association with no-reflow remains under-explored in vivo. Using longitudinal in vivo two-photon single-cell imaging over 7 days, we showed that 87% of pericytes constrict during cerebral ischaemia and remain constricted post reperfusion, and 50% of the pericyte population are acutely damaged. Moreover, we revealed ischaemic pericytes to be fundamentally implicated in capillary no-reflow by limiting and arresting blood flow within the first 24 h post stroke. Despite sustaining acute membrane damage, we observed that over half of all cortical pericytes survived ischaemia and responded to vasoactive stimuli, upregulated unique transcriptomic profiles and replicated. Finally, we demonstrated the delayed recovery of capillary diameter by ischaemic pericytes after reperfusion predicted vessel reconstriction in the subacute phase of stroke. Cumulatively, these findings demonstrate that surviving cortical pericytes remain both viable and promising therapeutic targets to counteract no-reflow after ischaemic stroke.

Pericytes: Problems and Promises for CNS Repair.

Microvascular complications are often associated with slow and progressive damage of various organs. Pericytes are multi-functional mural cells of the microcirculation that control blood flow, vascular permeability and homeostasis. Whereas accumulating evidence suggests that these cells are also implicated in a variety of diseases, pericytes represent promising targets that can be manipulated for therapeutic gain. Here, we review the role of pericytes in angiogenesis, blood-brain barrier (BBB) function, neuroinflammation, tissue fibrosis, axon regeneration failure, and neurodegeneration. In addition, we outline strategies altering pericyte behavior to point out problems and promises for axon regeneration and central nervous system (CNS) repair following injury or disease.