: Despite major advances in intravenous thrombolysis and endovascular thrombectomy, nearly half of patients with acute ischemic stroke fail to achieve functional recovery even after technically successful recanalization. The recanalization-reperfusion gap-the discordance between angiographic vessel opening and tissue-level perfusion recovery-has 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-recanalization resistance, no-reflow, and reperfusion injury-and discuss therapeutic opportunities that emerge from this framework. These include enzymatic neutrophil extracellular traps-targeting, 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.
Thromboinflammation in Acute Stroke: From Pathophysiological Challenges to Emerging Therapeutic Opportunities
Umberto Pensato;
2026-01-01
Abstract
: Despite major advances in intravenous thrombolysis and endovascular thrombectomy, nearly half of patients with acute ischemic stroke fail to achieve functional recovery even after technically successful recanalization. The recanalization-reperfusion gap-the discordance between angiographic vessel opening and tissue-level perfusion recovery-has 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-recanalization resistance, no-reflow, and reperfusion injury-and discuss therapeutic opportunities that emerge from this framework. These include enzymatic neutrophil extracellular traps-targeting, 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
