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Experimental evidence has emerged that local platelet activation contributes to inflammation and infarct formation in acute ischemic stroke (AIS) which awaits confirmation in human studies. We conducted a prospective observational study on 258 consecutive patients undergoing mechanical thrombectomy (MT) due to large-vessel-occlusion stroke of the anterior circulation (08/2018–05/2020). Intraprocedural microcatheter aspiration of 1 ml of local (occlusion condition) and systemic arterial blood samples (self-control) was performed according to a prespecified protocol. The samples were analyzed for differential leukocyte counts, platelet counts, and plasma levels of the platelet-derived neutrophil-activating chemokine C-X-C-motif ligand (CXCL) 4 (PF-4), the neutrophil attractant CXCL7 (NAP-2), and myeloperoxidase (MPO). The clinical-biological relevance of these variables was corroborated by specific associations with molecular-cellular, structural-radiological, hemodynamic, and clinical-functional parameters. Seventy consecutive patients fulfilling all predefined criteria entered analysis. Mean local CXCL4 (+ 39%: 571 vs 410 ng/ml,  P  = .0095) and CXCL7 (+ 9%: 693 vs 636 ng/ml,  P  = .013) concentrations were higher compared with self-controls. Local platelet counts were lower (− 10%: 347,582 vs 383,284/µl,  P  = .0052), whereas neutrophil counts were elevated (+ 10%: 6022 vs 5485/µl,  P  = 0.0027). Correlation analyses revealed associations between local platelet and neutrophil counts ( r  = 0.27,  P  = .034), and between CXCL7 and MPO ( r  = 0.24,  P  = .048). Local CXCL4 was associated with the angiographic degree of reperfusion following recanalization ( r  =  − 0.2523,  P  = .0479). Functional outcome at discharge correlated with local MPO concentrations ( r  = 0.3832,  P  = .0014) and platelet counts ( r  = 0.288,  P  = .0181). This study provides human evidence of cerebral platelet activation and platelet-neutrophil interactions during AIS and points to the relevance of per-ischemic thrombo-inflammatory mechanisms to impaired reperfusion and worse functional outcome following recanalization.

Platelet Activation and Chemokine Release Are Related to Local Neutrophil-Dominant Inflammation During Hyperacute Human Stroke