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Updated: Jun 29, 2026
Modeling Stroke in Mice: Permanent Coagulation of the Distal Middle Cerebral Artery
Published on: July 31, 2014
Mouse model of microembolic stroke and reperfusion
D N Atochin1, J C Murciano, Y Gürsoy-Ozdemir
1Cardiovascular Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Background And Purpose:
To test the role of fibrinolysis in stroke, we used a mouse model in which preformed 2.5- to 3-microm-diameter fibrin microemboli are injected into the cerebral circulation. The microemboli lodge in the downstream precapillary vasculature and are susceptible to fibrinolysis.
Methods:
We injected various doses of microemboli into the internal carotid artery in mice and characterized their distribution, effects on cerebral blood flow, neurological deficit, infarct area, and spontaneous dissolution. By comparing wild-type and tissue plasminogen activator (tPA) knockout (tPA-/-) mice, we analyzed the role of endogenous tPA in acute thrombotic stroke.
Results:
Microemboli cause dose-dependent brain injury. Although moderate doses of microemboli are followed by spontaneous reperfusion, they result in reproducible injury. Gene knockout of tPA markedly delays dissolution of cerebral emboli and restoration of blood flow and aggravates ischemic thrombotic infarction in the brain.
Conclusions:
We describe a microembolic model of stroke, in which degree of injury can be controlled by the dose of microemboli injected. Unlike vessel occlusion models, this model can be modulated to allow spontaneous fibrinolysis. Application to tPA-/- mice supports a key role of endogenous tPA in restoring cerebral blood flow and limiting infarct size after thrombosis.
Insights
This study demonstrates that endogenous tissue plasminogen activator (tPA) is crucial for dissolving cerebral microemboli and restoring blood flow, significantly limiting brain injury in a mouse stroke model.
Area of Science:
- Neuroscience
- Vascular Biology
- Thrombosis Research
Background:
- Stroke research often utilizes vessel occlusion models.
- A novel microembolic stroke model allows for controlled study of fibrinolysis.
- This model uses preformed fibrin microemboli susceptible to natural clot dissolution.
Purpose of the Study:
- To investigate the role of fibrinolysis in acute ischemic stroke.
- To establish and validate a mouse model of cerebral microembolism.
- To determine the contribution of endogenous tissue plasminogen activator (tPA) to stroke recovery.
Main Methods:
- Injection of calibrated fibrin microemboli into the mouse cerebral circulation.
- Assessment of microemboli distribution, cerebral blood flow, and neurological deficits.
- Comparison of wild-type mice with tissue plasminogen activator knockout (tPA-/-) mice.
Main Results:
- Microemboli induced dose-dependent brain injury and neurological deficits.
- Spontaneous reperfusion occurred with moderate microemboli doses, but injury persisted.
- tPA knockout significantly delayed emboli dissolution, blood flow restoration, and worsened brain infarction.
Conclusions:
- A reproducible mouse stroke model was developed using controlled microemboli dosage.
- This model allows for the investigation of spontaneous fibrinolysis, unlike vessel occlusion models.
- Endogenous tPA plays a critical role in resolving cerebral thrombosis and mitigating stroke damage.
