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Updated: Jul 14, 2026
A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
Published on: June 4, 2021
Microplasmin and tissue plasminogen activator: comparison of therapeutic effects in rat stroke model at
Feng Chen1, Yasuhiro Suzuki, Nobuo Nagai
1Department of Radiology, University Hospitals, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.
Purpose:
To prospectively compare therapeutic and hemorrhagic effects of microplasmin and tissue plasminogen activator (tPA) in stroke therapy by using multiparametric magnetic resonance (MR) imaging in a photothrombotic rat stroke model.
Materials And Methods:
The animal experiment complied with institutional regulations for laboratory animals. Stroke was induced in rats with photothrombotic occlusion of middle cerebral artery (MCA). T2-weighted, perfusion-weighted (PW), and diffusion-weighted (DW) MR imaging was performed 1 hour and 24 hours after occlusion. On the basis of PW and DW images at 1 hour, 49 rats with cortex and subcortex involvement and with perfusion-diffusion mismatch were randomly assigned into one of four groups: control group, group treated with 7.5 mg microplasmin, group treated with 10 mg/kg microplasmin, or group treated with 10 mg/kg tPA. Agents were intravenously injected 1.5 hours after occlusion. Infarct size and hemorrhagic transformation were assessed with MR imaging and histomorphologic findings. Neurologic deficit was scored. Measurements were statistically analyzed.
Results:
There were 13 rats in the control group, 13 in the 7.5 mg/kg microplasmin group, nine in the 10 mg/kg microplasmin group, and 14 in the 10 mg/kg tPA group. Despite similar baseline perfusion-diffusion mismatch, histochemically defined total infarct volume was reduced from 25% +/- 5 (standard deviation) in control group to 21% +/- 2, 20% +/- 4, and 20% +/- 5 in 7.5 mg/kg microplasmin, 10 mg/kg microplasmin, and tPA groups, respectively, as similarly shown on T2-weighted, DW, and PW images at 24 hours (P < .05). Cerebral hemorrhage rate at 24 hours was higher in tPA group than in the other three groups. Bederson score of neurologic deficits was significantly reduced in treated groups compared with that in control group.
Conclusion:
Perfusion-diffusion mismatch appeared useful in selecting candidates for thrombolytic therapy. Multiparametric MR imaging allowed noninvasive assessment of effects of microplasmin and tPA in rats; microplasmin had a significantly lower hemorrhagic rate.
Insights
Microplasmin and tissue plasminogen activator (tPA) reduced stroke infarct volume in rats. Microplasmin demonstrated a significantly lower rate of cerebral hemorrhage compared to tPA.
Area of Science:
- Neuroscience
- Radiology
- Pharmacology
Background:
- Stroke is a leading cause of death and disability worldwide.
- Effective thrombolytic therapy is crucial for improving stroke outcomes.
- Tissue plasminogen activator (tPA) is the current standard, but carries risks of hemorrhage.
Purpose of the Study:
- To compare the therapeutic and hemorrhagic effects of microplasmin and tPA in a rat stroke model.
- To evaluate the utility of multiparametric MRI in assessing treatment response.
- To investigate microplasmin as a potential alternative thrombolytic agent.
Main Methods:
- A photothrombotic middle cerebral artery occlusion model was used in rats.
- Multiparametric MRI (T2-weighted, perfusion-weighted, diffusion-weighted) was performed.
- Rats with perfusion-diffusion mismatch were randomized to receive microplasmin, tPA, or control treatment.
Main Results:
- Both microplasmin and tPA significantly reduced infarct volume compared to controls.
- The cerebral hemorrhage rate was significantly lower in microplasmin-treated groups than in the tPA group.
- Neurologic deficit scores were significantly improved in all treated groups.
Conclusions:
- Perfusion-diffusion mismatch identified by MRI is a valuable tool for selecting stroke patients for thrombolytic therapy.
- Multiparametric MRI enables noninvasive assessment of thrombolytic treatment effects.
- Microplasmin shows promise as a thrombolytic agent with a reduced hemorrhagic risk compared to tPA.
