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Identification of key molecules that regulate the transformation of resting Mi\/M\u03a6 could aid in the development of innovative therapies for ischemic stroke. The transcription factor signal transducer and activator of transduction 1 (STAT1) has been found to contribute to acute neuronal death (in the first 24\u00a0h) following ischemic stroke, but its effects on Mi\/M\u03a6 and influence on long-term stroke outcomes have yet to be determined.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We generated mice with tamoxifen-induced, Mi\/M\u03a6-specific knockout (mKO) of STAT1 driven by Cx3cr1<jats:sup>CreER<\/jats:sup>. Expression of STAT1 was examined in the brain by flow cytometry and RNA sequencing after ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). The impact of STAT1 mKO on neuronal cell death, Mi\/M\u03a6 phenotype, and brain inflammation profiles were examined 3\u20135\u00a0days after MCAO. Neurological deficits and the integrity of gray and white matter were assessed for 5\u00a0weeks after MCAO by various neurobehavioral tests and immunohistochemistry.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>STAT1 was activated in Mi\/M\u03a6 at the subacute stage (3\u00a0days) after MCAO. Selective deletion of STAT1 in Mi\/M\u03a6 did not alter neuronal cell death or infarct size at 24\u00a0h after MCAO, but attenuated Mi\/M\u03a6 release of high mobility group box 1 and increased arginase 1-producing Mi\/M\u03a6 3d after MCAO, suggesting boosted inflammation-resolving responses of Mi\/M\u03a6. As a result, STAT1 mKO mice had mitigated brain inflammation at the subacute stage after MCAO and less white matter injury in the long term. Importantly, STAT1 mKO was sufficient to improve functional recovery for at least 5\u00a0weeks after MCAO in both male and female mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Mi\/M\u03a6-targeted STAT1 KO does not provide immediate neuroprotection but augments inflammation-resolving actions of Mi\/M\u03a6, thereby facilitating long-term functional recovery after stroke. STAT1 is, therefore, a promising therapeutic target to harness beneficial Mi\/M\u03a6 responses and improve long-term outcomes after ischemic stroke.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-023-02860-4","type":"journal-article","created":{"date-parts":[[2023,7,29]],"date-time":"2023-07-29T11:02:39Z","timestamp":1690628559000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Targeted ablation of signal transducer and activator of transduction 1 alleviates inflammation by microglia\/macrophages and promotes long-term recovery after ischemic stroke"],"prefix":"10.1186","volume":"20","author":[{"given":"Wenxuan","family":"Han","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjian","family":"Pu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sicheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyue","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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