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27 reviewsSUMMARYStroke is a major cause of disability. Astrocytes respond to stroke in a gradated manner, but details of thatresponse and its consequences for tissue repair are poorly understood, particularly across brain regions andstroke subtypes. We identified phenotypically and morphologically distinct zones of reactive astrocytes inmouse models of cortical and white matter stroke. Zone-specific transcriptomic analyses revealed thatcortical, but not white matter, astrocytes upregulated transcriptional programs promoting the formation ofnew blood vessels, a key repair mechanism. Viral gain- and loss-of-function strategies showed that astrocytic Lamc1, in particular, is an endogenous mechanism by which cortical, but not white matter, astrocytesdrive remodeling of larger-caliber brain microvessels. Exogenous induction of Lamc1 in white matter astrocytes improved vessel remodeling and repair and triggered differential T cell infiltration post stroke. Astrocytesubpopulations show region-specific responses to ischemia that can be leveraged to promote repair,including astrocyte-induced vascular remodeling.