Immunological insights into acute ischemic stroke From inflammation to thrombosis

Acute ischemic stroke (AIS), particularly stroke caused by large vessel occlusion, remains a major cause of death and long-term disability. Although intravenous thrombolysis and endovascular treatment have markedly improved reperfusion, successful recanalization does not always result in neurological recovery. This discrepancy suggests that mechanisms beyond vascular obstruction contribute substantially to tissue injury and clinical outcomes.
Increasing evidence indicates that AIS is driven not only by impaired blood flow but also by immunothrombosis and thromboinflammation, involving reciprocal interactions among coagulation, complement activation, circulating inflammatory responses, and immune-cell recruitment within thrombi. These processes may influence thrombus formation, treatment response, reperfusion injury, and recovery. Importantly, they may differ across stroke etiologies, particularly between large-artery atherosclerosis and cardioembolism. However, the clinical relevance, temporal evolution, and etiological specificity of these immune mechanisms remain incompletely understood.
This thesis investigates the immune–thrombosis–inflammation axis in AIS at the systemic and local levels while also examining its temporal dynamics. It assesses the prognostic relevance of systemic inflammation, characterizes the temporal dynamics of complement activation after stroke, and evaluates the immune-cell composition of retrieved thrombi in relation to stroke etiology, procedural characteristics, reperfusion, and functional outcomes.
By integrating these complementary perspectives, this thesis advances a broader understanding of AIS beyond mechanical vessel occlusion alone. It provides a conceptual framework linking systemic inflammation, complement activation, and thrombus immunobiology and supports the development of more precise biomarkers and adjunctive therapies targeting immune and inflammatory pathways in the reperfusion era.