The role of nonneuronal cells in the resolution of cerebral ischemia remains to be fully understood. To decode key molecular and cellular processes that occur after ischemia, we performed spatial and single-cell transcriptomic profiling of the male mouse brain during the first week of injury. Cortical gene expression was severely disrupted, defined by inflammation and cell death in the lesion core, and glial scar formation orchestrated by multiple cell types on the periphery. The glial scar was identified as a zone with intense cell-cell communication, with prominent ApoE-Trem2 signaling pathway modulating microglial activation. For each of the three major glial populations, an inflammatory-responsive state, resembling the reactive states observed in neurodegenerative contexts, was observed. The recovered spectrum of ischemia-induced oligodendrocyte states supports the emerging hypothesis that oligodendrocytes actively respond to and modulate the neuroinflammatory stimulus. The findings are further supported by analysis of other spatial transcriptomic datasets from different mouse models of ischemic brain injury. Collectively, we present a landmark transcriptomic dataset accompanied by interactive visualization that provides a comprehensive view of spatiotemporal organization of processes in the postischemic mouse brain.

Department of Cellular Neurophysiology Institute of Experimental Medicine of the Czech Academy of Sciences Prague 14220 Czech Republic

Department of Informatics and Chemistry Faculty of Chemical Technology University of Chemistry and Technology Prague 16000 Czech Republic

Department of Radiodiagnostic and Interventional Radiology Institute of Clinical and Experimental Medicine Prague 14021 Czech Republic

Faculty of Health Studies Technical University of Liberec Liberec 46001 Czech Republic

Laboratory of Gene Expression Institute of Biotechnology of the Czech Academy of Sciences Vestec 25250 Czech Republic

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Spatiotemporal transcriptomic map of glial cell response in a mouse model of acute brain ischemia