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Updated: Jan 19, 2026
A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
Published on: June 4, 2021
Acute ischemic stroke thrombi have an outer shell that impairs fibrinolysis
Lucas Di Meglio1, Jean-Philippe Desilles1, Véronique Ollivier1
1From U1148 Institut National de la Santé et de la Recherche Médicale (INSERM) (L.D.M., J.-P.D., V.O., M.S.N., S.D.M., C.D., S.L., M.-C.B., J.-B.M., M.J.-P., B.H.-T.-N., M.M.), Laboratory of Vascular Translational Science, Sorbonne Paris Cité, Université Paris Diderot; Department of Interventional Neuroradiology (J.-P.D., R.B., M.P., M.M.), Rothschild Foundation Hospital, Paris; and Toulouse University Medical Center (J.-M.O.), France.
Objectives:
Thrombi responsible for large vessel occlusion (LVO) in the setting of acute ischemic stroke (AIS) are characterized by a low recanalization rate after IV thrombolysis. To test whether AIS thrombi have inherent common features that limit their susceptibility to thrombolysis, we analyzed the composition and ultrastructural organization of AIS thrombi causing LVO.
Methods:
A total of 199 endovascular thrombectomy-retrieved thrombi were analyzed by immunohistology and scanning electron microscopy (SEM) and subjected to ex vivo thrombolysis assay. The relationship between thrombus organization and thrombolysis resistance was further investigated in vitro using thrombus produced by recalcification of citrated whole blood.
Results:
SEM and immunohistology analyses revealed that, although AIS thrombus composition and organization was highly heterogeneous, AIS thrombi shared a common remarkable structural feature in the form of an outer shell made of densely compacted thrombus components including fibrin, von Willebrand factor, and aggregated platelets. In vitro thrombosis experiments using human blood indicated that platelets were essential to the formation of the thrombus outer shell. Finally, in both AIS and in vitro thrombi, the thrombus outer shell showed a decreased susceptibility to tissue plasminogen activator-mediated thrombolysis as compared to the thrombus inner core.
Interpretation:
Irrespective of their etiology and despite their heterogeneity, intracranial thrombi causing LVO have a core shell structure that influences their susceptibility to thrombolysis.
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