Related Experiment Video
Updated: May 5, 2026
Modeling Stroke in Mice: Focal Cortical Lesions by Photothrombosis
Published on: May 6, 2021
Imaging of experimental stroke models
Marc Fisher1, Bernt Tore Bråtane
1Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA, fisherm@ummhc.org.
Abstract:
The ischemic penumbra is the target of acute stroke therapy. It can be approximated on diffusion/perfusion MRI as the ischemic region with abnormal perfusion and normal diffusion imaging. Using arterial spin labeling perfusion MRI and diffusion MRI, our group has studied the evolution of the diffusion/perfusion mismatch in rat stroke models. Additionally, we have evaluated the effects of high-flow oxygen on the natural history of penumbral evolution, demonstrating that high-flow oxygen "freezes" the evolution of the mismatch and allows for later beneficial use of intravenous tissue plasminogen activator (tPA). Two neuroprotective drugs, Granulocyte colony stimulating factor and a PSD95 inhibitor both impeded the evolution of the mismatch into infarcted tissue in vivo and by histological analysis. Employing a novel technique of clot imaging, our group was able to demonstrate that the combination of tPA plus Annexin-2 was superior to tPA alone in dissolving an embolus and also in reducing the extent of hypoperfused brain tissue of perfusion imaging. The use of these advanced MRI techniques in animal experiments will help to advance clinical imaging of the ischemic penumbra and hopefully contribute to the extension of the therapeutic time window in stroke patients.
Insights
High-flow oxygen and neuroprotective drugs can preserve the ischemic penumbra, the target of acute stroke therapy. Advanced MRI techniques in animal models may extend the therapeutic window for stroke patients.
Area of Science:
- Neuroscience
- Radiology
- Pharmacology
Background:
- The ischemic penumbra, a region of brain tissue at risk during stroke, is the primary target for acute stroke therapies.
- Diffusion/perfusion MRI can approximate the penumbra by identifying areas with abnormal perfusion and normal diffusion.
Purpose of the Study:
- To investigate the evolution of the diffusion/perfusion mismatch in rat stroke models.
- To evaluate the effects of high-flow oxygen and neuroprotective agents on penumbral evolution.
- To assess novel clot imaging techniques for stroke treatment.
Main Methods:
- Utilized arterial spin labeling perfusion MRI and diffusion MRI in rat stroke models.
- Administered high-flow oxygen and two neuroprotective drugs (Granulocyte colony stimulating factor, PSD95 inhibitor).
- Employed a novel clot imaging technique combined with tPA and Annexin-2.
Main Results:
- High-flow oxygen "froze" penumbral evolution, extending the therapeutic window for intravenous tissue plasminogen activator (tPA).
- Neuroprotective drugs impeded the evolution of the diffusion/perfusion mismatch into infarction.
- The combination of tPA plus Annexin-2 was more effective than tPA alone in dissolving emboli and reducing hypoperfused brain tissue.
Conclusions:
- Advanced MRI techniques in animal models are crucial for understanding penumbral dynamics.
- Interventions like high-flow oxygen and specific drugs show potential in preserving the ischemic penumbra.
- These findings may contribute to extending the therapeutic time window for acute ischemic stroke patients.
