BBB recovery after stroke by self-replenishing E-pericytes transdifferentiated from local endothelial cells

Abstract

AbstractIschemic stroke causes a significant amount of cell death, including pericytes. Chronic perfused phase of ischemic stroke, the number of pericytes increases, and limited research has been explorated on the reasons for the recovery of pericytes. By genetic tracing, we identified ECs undergoing cell-fate changing, through TGFb-pSMAD3-EndoMT pathway transdifferentiation, into pericytes (E-pericytes). Some of the migrating E-pericytes induced by stroke are derived from detached ECs. The E-pericytes can integrate into vasculature again, suggesting ischemic brains can recycle ECs from unfunctional vessels to replenish lost pericytes as an innate self-maintenance program sustaining repair phenomena. We also found E-pericytes promotes BBB restoration, increases angiogenesis and restores cerebral blood flow(CBF), resulting more neurons survive and accelerating behavioral rehabilitation.