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The recanalization-reperfusion gap\u2014the discordance between angiographic vessel opening and tissue-level perfusion recovery\u2014has brought thromboinflammation, the pathological interplay of coagulation and innate immunity, to the forefront of stroke biology. Neutrophil extracellular traps, platelet-leukocyte aggregates, complement activation, and vessel wall inflammation render clots resistant to lysis, promote microvascular obstruction and the no-reflow phenomenon, and amplify ischemia-reperfusion injury. These insights reframe stroke not solely as a problem of reopening arteries, but as an inflammatory disorder in which thrombus biology, microcirculatory flow, and inflammatory injury determine outcome. In this review, we outline the key thromboinflammatory challenges\u2014recanalization resistance, no-reflow, and reperfusion injury\u2014and discuss therapeutic opportunities that emerge from this framework. These include enzymatic neutrophil extracellular traps\u2013targeting, adjunctive anti-inflammatory agents, biomarker-guided precision approaches, and novel device technologies that exploit or mitigate thrombus biology. Collectively, these strategies support a paradigm shift in stroke care: from procedure-focused reperfusion to biologically informed interventions that integrate vascular and immune determinants of outcome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.125.051476","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T09:00:43Z","timestamp":1779872443000},"page":"1885-1895","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Thromboinflammation in Acute Stroke: From Pathophysiological Challenges to Emerging Therapeutic Opportunities"],"prefix":"10.1161","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4042-4735","authenticated-orcid":true,"given":"Umberto","family":"Pensato","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Milan, Italy (U.P.)."},{"name":"Department of Neurology, Istituto di Ricovero e 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