Abstract
SUMMARYBrain 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. In this study, we show that reactive astrocytes are crucial for vascular repair and remodeling after ischemic stroke in mice. Analysis of astrocytic gene expression data reveals substantial activation of transcriptional programs related to vascular remodeling after stroke. In vivo two-photon imaging provides evidence of astrocytes contacting newly formed vessels in cortex surrounding photothrombotic infarcts. Chemogenetic ablation of a subset of reactive astrocytes after stroke dramatically impairs vascular and extracellular matrix remodeling. This disruption of vascular repair is accompanied by prolonged blood flow deficits, exacerbated vascular permeability, ongoing cell death, and worsened motor recovery. In contrast, vascular structure in the non-ischemic brain is unaffected by focal astrocyte ablation. These findings position reactive astrocytes as critical cellular mediators of functionally important vascular remodeling during neural repair.
Highlights
Reorganization of residual neural tissue underlies recovery after brain injury
Stroke activates transcriptional programs relevant for vascular remodeling in reactive astrocytes We analyzed a reactive astrocyte transcriptome resource (GEO: GSE35338) (Zamanian et al, 2012) to elucidate functional changes in reactive astrocytes during the first week after experimental stroke, which is a time of significant vascular plasticity and repair (Williamson et al, 2020)
These data indicate that upregulation of genes relating to vascular growth and repair are a central component of the transcriptional programs activated in reactive astrocytes after ischemia
Summary
Reorganization of residual neural tissue underlies recovery after brain injury. Stroke triggers morphological and functional changes across cell types, especially near the infarct (Allegra Mascaro et al, 2019; Brown et al, 2007; Kim et al, 2018). Vascular remodeling in peri-infarct cortex occurs largely during the first 2 weeks post-stroke in rodent models, and it is characterized by concurrent formation and pruning of capillary segments to help restore blood flow to residual tissue (Williamson et al, 2020). This process contributes to behavioral recovery and is thought to be crucial for resolving metabolic failure in surviving tissue and re-establishing a microenvironment that can support other aspects of neural repair (Mostany et al, 2010; Rust et al, 2019a; Williamson et al, 2020). The factors that mediate vascular remodeling after cerebral ischemia are incompletely understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
