Related Experiment Video
Updated: May 4, 2026
A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
Published on: June 4, 2021
Lack of secondary microthrombosis after thrombin-induced stroke in mice and non-human primates
M Gauberti1, S Martinez de Lizarrondo, C Orset
1Inserm UMR-S U919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Inserm, Université Caen Basse-Normandie, GIP Cyceron, Caen, France.
Background:
Secondary microthrombosis is a major pathophysiologic mechanism leading to brain damage following transient mechanical vascular occlusion (TMVO), the most widely used experimental stroke model. Whether secondary microthrombosis also occurs in non-TMVO stroke models represents an important issue for clinical translation of antimicrothrombosis therapeutic strategies.
Objectives:
To assess the occurrence and the pathogenic role of secondary microthrombosis in two thrombin-induced stroke models in mice and non-human primates (Macaca mulatta).
Methods:
Stroke was induced in mice and non-human primates by intra-arterial administration of recombinant thrombin. This method induces the formation of a fibrin-rich thrombus, which is spontaneously dissolved in the following hours by the endogenous fibrinolytic system. Perfusion-weighted imaging and fluorescent-lectin microangiography were performed after recanalization to detect secondary microthrombosis. Moreover, to investigate its pathogenic role, thrombin-induced stroke was induced in bradykinin receptor B1 (B1R) knockout mice, which are protected from the thromboinflammation responsible for secondary microthrombosis in TMVO models.
Results:
Reperfusion was stable and complete in all mice and non-human primates tested, revealing no secondary decrease in cerebral blood flow. No evidence of secondary microthrombosis was found in the two models. Accordingly, deficiency in B1R did not protect the mice from brain damage after thrombin-induced stroke.
Conclusions:
Our data demonstrate that secondary microthrombosis does not occur after thrombin-induced stroke. In view of this, the pathophysiologic roles of hematologic players promoting or protecting against secondary microthrombosis (such as factor XII, von Willebrand factor, and T cells) deserve to be re-evaluated in non-TMVO stroke models.
Insights
Secondary microthrombosis does not occur in thrombin-induced stroke models. This finding suggests re-evaluating the roles of certain blood factors in non-transient mechanical vascular occlusion stroke models.
Area of Science:
- Neuroscience
- Vascular Biology
- Stroke Research
Background:
- Secondary microthrombosis is a key factor in brain damage in transient mechanical vascular occlusion (TMVO) stroke models.
- Its occurrence in other stroke models is crucial for translating anti-microthrombosis therapies.
Purpose of the Study:
- To investigate secondary microthrombosis in thrombin-induced stroke models in mice and non-human primates.
- To determine the pathogenic role of secondary microthrombosis in these models.
Main Methods:
- Stroke was induced by intra-arterial thrombin administration in mice and non-human primates.
- Perfusion-weighted imaging and microangiography were used to detect secondary microthrombosis post-recanalization.
- Bradykinin receptor B1 knockout mice were used to assess the role of thromboinflammation.
Main Results:
- Complete reperfusion was observed in all animals, with no secondary decrease in cerebral blood flow.
- No evidence of secondary microthrombosis was detected in either model.
- Bradykinin receptor B1 deficiency did not protect against brain damage in thrombin-induced stroke.
Conclusions:
- Secondary microthrombosis does not appear to be a factor in thrombin-induced stroke models.
- The roles of factors like Factor XII, von Willebrand factor, and T cells in non-TMVO stroke models require re-evaluation.
