RESUMEN
INTRODUCTION: Achieving first pass recanalization (FPR) has become the primary procedural objective during thrombectomy in acute ischemic stroke patients as it correlates with the best clinical outcome. Understanding factors contributing to FPR failures is essential to enhance FPR success rates. As the central target of thrombectomy, the thrombus itself may be a significant factor influencing FPR. This study aims to investigate the association between thrombus composition and FPR success rates. METHODS: In total, thrombi from 267 ischemic stroke patients were collected in the AZ Groeninge Hospital (Kortrijk, Belgium). Thrombus composition was determined via detailed histological analysis of red blood cells (RBC), fibrin, von Willebrand factor, platelets, leukocytes, citrullinated histone 3 (marker for neutrophil extracellular traps) and intra- and extracellular DNA. FPR was defined as obtaining a modified Thrombolysis in Cerebral Ischemia (mTICI) score of 2c/3 after the first pass. RESULTS: An mTICI score of 2c/3 was obtained in 180 patients, which was achieved via a successful FPR procedure in 126 cases or after multiple passes in 54 cases. Interestingly, thrombi from FPR cases had a different composition than thrombi that needed multiple passes to obtain mTICI 2c/3. FPR thrombi contained significantly more RBC (p=0.0264), less fibrin (p=0.0196) and less extracellular DNA (p=0.0457). CONCLUSIONS: Our results indicate that thrombi characterized by lower RBC content, higher fibrin levels, and increased extracellular DNA are less likely to result in a FPR. These results are important to guide future research aiming at improving procedures or technologies to obtain FPR-rates in RBC-poor thrombi.
RESUMEN
Background: Thromboinflammatory processes modulate the complex pathophysiology of cerebral ischemia-reperfusion (I/R) injury in ischemic stroke, but the exact underlying mechanisms remain poorly understood. Emerging evidence indicates that neutrophil extracellular traps (NETs) might play an important role in the thromboinflammatory cascade. In addition, the link between von Willebrand factor (VWF) and neutrophil recruitment in the ischemic brain might promote thromboinflammation, possibly by the formation of NETs. Objectives: To study NET formation in a murine model of cerebral I/R injury in ischemic stroke. Methods: The filament-induced transient middle cerebral artery occlusion model was used to induce 60 minutes of focal cerebral ischemia after which reperfusion was allowed. At different time points postischemia, NETs were identified in the ischemic mouse brain using quantitative immunofluorescence microscopy. Results: NETs could be identified in the ipsilateral brain hemisphere. Interestingly, NETs could already be detected at 6 hours poststroke. Their presence increased at 12 hours, was highest at 24 hours, and decreased again 48 hours postischemia. Remarkably, NETs were predominantly localized within the brain vasculature postischemia, suggesting that NETs play a role in secondary microthrombosis. Strikingly, NET formation was significantly decreased in VWF-deficient mice compared to littermate wild-type mice 24 hours postischemia, indicating a possible role for VWF in promoting NETosis in the ischemic brain. Conclusion: This study identified the spatiotemporal profile of NET formation in a mouse model of cerebral I/R injury in ischemic stroke. NETs, potentially in combination with VWF, might be attractive targets for the development of novel therapeutic strategies in ischemic stroke treatment.