Reactive Astrocytes Facilitate Vascular Repair and Remodeling after Stroke

Abstract

Brain injury causes astrocytes to assume a reactive state that is essential for early tissue protection, but how reactive astrocytes affect later reparative processes is incompletely understood. Here we show that reactive astrocytes are crucial for vascular repair and remodeling after ischemic stroke in mice. Analysis of astrocytic gene expression data revealed substantial activation of transcriptional programs related to vascular remodeling after stroke. In vivo 2-photon imaging provided evidence of astrocytes contacting newly formed vessels in cortex surrounding photothrombotic infarcts. Chemogenetic ablation of a subset of reactive astrocytes after stroke dramatically impaired vascular and extracellular matrix remodeling. This disruption of vascular repair was accompanied by prolonged blood flow deficits, exacerbated vascular permeability, ongoing cell death, and worsened motor recovery. By contrast, vascular structure in the non-ischemic brain was unaffected by focal astrocyte ablation. These findings position reactive astrocytes as critical cellular mediators of functionally important vascular remodeling during neural repair.