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Recent studies have shown that stroke development and prognosis are closely related to abnormal tryptophan metabolism. Here, significant downregulation of 3\u2010hydroxy\u2010kynurenamine (3\u2010HKA) in stroke patients and animal models is identified. Supplementation with 3\u2010HKA improved long\u2010term neurological recovery, reduced infarct volume, and increased ipsilateral cerebral blood flow after distal middle cerebral artery occlusion (MCAO). 3\u2010HKA promoted angiogenesis, functional blood vessel formation, and blood\u2010brain barrier (BBB) repair. Moreover, 3\u2010HKA inhibited A1\u2010like (neurotoxic) astrocyte activation but promoted A2\u2010like (neuroprotective) astrocyte polarization. Proteomic analysis revealed that 3\u2010HKA inhibited AIM2 inflammasome activation after stroke, and co\u2010labeling studies indicated that AIM2 expression typically increased in astrocytes at 7 and 14 days after stroke. Consistently, in co\u2010cultures of primary mouse brain microvascular endothelial cells and astrocytes, 3\u2010HKA promoted angiogenesis after oxygen\u2010glucose deprivation (OGD). AIM2 overexpression in astrocytes abrogated 3\u2010HKA\u2010driven vascular remodeling in vitro and in vivo, suggesting that 3\u2010HKA may regulate astrocyte\u2010mediated vascular remodeling by impeding AIM2 inflammasome activation. In conclusion, 3\u2010HKA may promote post\u2010stroke vascular remodeling by regulating A1\/A2 astrocyte activation, thereby improving long\u2010term neurological recovery, suggesting that supplementation with 3\u2010HKA may be an efficient therapy for stroke.<\/jats:p>","DOI":"10.1002\/advs.202412667","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T10:18:57Z","timestamp":1737713937000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["3\u2010HKA Promotes Vascular Remodeling After Stroke by Modulating the Activation of A1\/A2 Reactive Astrocytes"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7796-5703","authenticated-orcid":false,"given":"Jun\u2010Min","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology Beijing Tiantan Hospital Capital Medical University  Beijing 100070 China"},{"name":"Department of 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