Comprehensive immunological profiling of acute ischemic stroke during mechanical thrombectomy: myeloid cell activation and molecular signatures in blood and thrombus.

Background: Acute ischemic stroke (AIS) induces a complex local and systemic inflammatory response; however, most studies rely solely on peripheral blood, providing an incomplete view of immune activity at the occlusion site and within the thrombus. Objective: To characterize immune activation and transcriptomic signatures of myeloid cells across three compartments-arterial blood at the occlusion site, peripheral blood, and thrombus-and to evaluate their associations with radiological and clinical outcomes following mechanical thrombectomy. Methods: This prospective, single-center study will include AIS patients treated with mechanical thrombectomy. Matched arterial, peripheral, and thrombus samples will undergo spectral flow cytometry, cytokine profiling, cell-free DNA (cfDNA) quantification, microscopy, and RNA sequencing. Immune and molecular readouts will be correlated with clinical scores (NIHSS, mRS), imaging markers (e.g., hyperdense middle cerebral artery sign [HMCAS]), and procedural outcomes (TICI score, number of passes). Significance: Integrating local and systemic immune profiles with clinical and radiological parameters may identify biomarkers predictive of thrombectomy efficacy and functional recovery, thereby supporting precision-medicine approaches in AIS. Clinical trial registration: www.ClinicalTrials.gov.