Early loss of pericytes and perivascular stromal cell-induced scar formation after stroke




Fernandez-Klett, Francisco
Potas, Jason
Hilpert, Diana
Blazej, Katja
Radke, Josefine
Huck, Jojanneke
Engel, Odilo
Stenzel, Werner
Genove, Guillem
Priller, Josef

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Nature Publishing Group


Despite its limited regenerative capacity, the central nervous system (CNS) shares more repair mechanisms with peripheral tissues than previously recognized. Scar formation is a ubiquitous healing mechanism aimed at patching tissue defects via the generation of fibrous extracellular matrix (ECM). This process, orchestrated by stromal cells, can unfavorably affect the capacity of tissues to restore function. Vascular mural cells have been found to contribute to scarring after spinal cord injury. In the case of stroke, little is known about the responses of pericytes (PCs) and stromal cells. Here, we show that capillary PCs are rapidly lost after cerebral ischemia in both experimental and human stroke. Coincident with this loss is a massive proliferation of resident platelet-derived growth factor receptor beta (PDGFRβ) + and CD105 + stromal cells, which originate from the neurovascular unit and deposit ECM in the ischemic mouse brain. The presence of PDGFRβ + stromal cells demarcates a fibrotic, contracted, and macrophage-laden lesion core from the rim of hypertrophic astroglia in both experimental and human stroke. We suggest that a previously unrecognized population of CNS-resident stromal cells drives a dynamic process of scarring after cerebral ischemia, which appears distinct from the glial scar and represents a novel target for regenerative stroke therapies.



Keywords: endoglin; platelet derived growth factor beta receptor; animal experiment; animal model; animal tissue; article; brain ischemia; cell loss; cell proliferation; controlled study; extracellular matrix; human; human tissue; macroglia; mouse; nonhuman; pericy cerebral ischemia; extracellular matrix; fibrosis; neurovascular unit; pericyte; platelet-derived growth factor receptor beta



Journal of Cerebral Blood Flow and Metabolism


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