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.

• Keywords
• glia, ischemic stroke, neuroinflammation, single-cell transcriptomics, spatial transcriptomics,
• MeSH
• Brain Ischemia * genetics   metabolism   pathology   MeSH
• Membrane Glycoproteins metabolism   genetics   MeSH
• Microglia metabolism   MeSH
• Disease Models, Animal * MeSH
• Brain metabolism   pathology   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Neuroglia * metabolism   MeSH
• Oligodendroglia metabolism   MeSH
• Receptors, Immunologic MeSH
• Signal Transduction MeSH
• Gene Expression Profiling MeSH
• Transcriptome * MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Membrane Glycoproteins MeSH
• Receptors, Immunologic MeSH
• Trem2 protein, mouse MeSH Browser