From recanalization to recovery: inflammation and futile reperfusion after mechanical thrombectomy

Mechanical thrombectomy (MT) has markedly improved reperfusion outcomes in patients with acute ischemic stroke caused by large-vessel occlusion. However, successful angiographic reperfusion does not invariably translate into functional independence. Poor functional outcome despite successful angiographic reperfusion is commonly described as futile reperfusion. This clinical-angiographic mismatch may reflect persistent tissue injury, including inflammatory injury, alongside pretreatment damage and other determinants of outcome. Experimental findings and clinical associations implicate persistent inflammatory activation, thrombo-inflammation, endothelial dysfunction, microvascular no-reflow, and blood-brain barrier disruption as contributors to secondary tissue injury after MT. Here, we examine potential inflammatory contributions to futile reperfusion and consider how inflammatory biomarkers might inform risk stratification after MT. Ischemia activates microglia, endothelial cells, platelets, complement pathways, and circulating immune cells. Subsequent reperfusion may amplify oxidative stress, cytokine signaling, neutrophil-endothelial interactions, neutrophil extracellular trap formation, matrix metalloproteinase activity, and barrier failure. Together, these processes can promote microvascular obstruction, cerebral edema, hemorrhagic transformation, infarct growth, and impaired neurological recovery despite successful angiographic reperfusion. Among circulating biomarkers, the neutrophil-to-lymphocyte ratio has been studied repeatedly, alongside platelet-to-lymphocyte ratio, systemic immune-inflammation index, systemic inflammation response index, interleukin-6, matrix metalloproteinase-9, and other molecular markers. Their specificity, incremental predictive value, and clinical utility require further validation in standardized thrombectomy cohorts. We therefore view inflammation as a plausible biological link between macrovascular reperfusion and persistent tissue-level injury after MT. From a translational perspective, the immediate priorities are to standardize sampling protocols, characterize dynamic inflammatory trajectories, develop multimodal prediction models, and test biomarker-guided therapeutic strategies.