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Morphology and distribution of microglia were assessed via immunofluorescence (IF) staining and electron microscopy. Single\u2010cell RNA\u2010sequencing (scRNA\u2010seq) analyzed the activation characteristics of infiltrating CD8<jats:sup>+<\/jats:sup> T cells and the transcriptional heterogeneity of microglia in ECM. In\u00a0vitro, ECM\u2010associated microglia were induced by TNF\u03b1, IFN\u03b3, and parasite\u2010infected red blood cells (pRBCs). The interaction between microglia and CD8<jats:sup>+<\/jats:sup> T cells was explored in co\u2010culture systems through transwell assay, adhesion assay, and cytotoxicity test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vivo, microglia were aggregated in the brainstem and olfactory bulb in the ECM brain, regions that exhibited more severe pathological injury. The transcriptional characteristics of ECM microglia distinguished from physiological microglia and exhibit morphological heterogeneity in the ECM brain. Infiltrating CD8<jats:sup>+<\/jats:sup> T cells in the ECM brainstem exhibit sustained activation characteristics associated with microglia interaction. Based on subcluster analysis, a unique subtype of ECM\u2010associated microglia was identified, characterized by CXCL10<jats:sup>high<\/jats:sup>TNF\u03b1<jats:sup>high<\/jats:sup>Ki67<jats:sup>+<\/jats:sup>. These microglia mediated the recruitment and sustained activation of CD8<jats:sup>+<\/jats:sup> T cells through persistent interactions in co\u2010culture systems.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study identified an ECM\u2010associated microglia subtype and explored its interaction with CD8<jats:sup>+<\/jats:sup> T cells, which deepened the understanding of the multifaceted role of microglia in the pathogenesis of CM neuroinflammation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70425","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T23:57:36Z","timestamp":1748908656000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>CXCL10<sup>high<\/sup>TNF\u03b1<sup>high<\/sup>Ki67<\/scp><sup>+<\/sup> Microglia Recruit and Activate <scp>CD8<\/scp><sup>+<\/sup> T Cells in the Brainstem During Experimental Cerebral 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