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Effects of microplasmin on recovery in a rat embolic stroke model
Rune Skovgaard Rasmussen1, Karsten Overgaard, Steve Pakola
1Copenhagen Experimental Stroke Unit, Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen North, Denmark. rsr@nepa.ku.dk
Objectives:
The purpose of the present study was to examine the effects of microplasmin on behavioral performance and infarct volume after middle cerebral artery occlusion (MCAO) in rats. Some experiments support that microplasmin may have neuroprotective and thrombolytic properties.
Methods:
Eighty rats underwent surgery and were embolized in the right carotid territory with a fibrin-rich embolus and randomly assigned into three groups: 5 mg/kg microplasmin, 10 mg/kg microplasmin or saline (control). Groups treated with microplasmin received 50% bolus injection 10 minutes after embolization and 50% continuous infusion during the following hour. Animals from all groups were trained to obtain high baseline scores in Montoya's staircase test before embolization and were retested during 7-14 days after surgery.
Results:
When pre-maturely dead animals were excluded, no differences were observed among groups regarding infarct volumes. Furthermore, mortality was significantly lower in Group 1 than in Group 2 (p<0.05) and when performances were evaluated 7-14 days after surgery, Group 1 was significantly better than Group 2 concerning fine motor performance (p<0.05) and also achieved more normal bodyweight (p<0.05).
Discussion:
Among surviving animals, 5 mg/kg microplasmin treatment had no effect compared to saline-treated control animals; 5 mg/kg microplasmin reduced mortality and improved both behavioral rehabilitation and bodyweight compared to 10 mg/kg microplasmin treatment, while saline-treated animals did not differ from animals treated with 10 mg/kg microplasmin. Overall, these results indicate a potential beneficial effect of 5 mg/kg microplasmin treatment, while 10 mg/kg may worsen outcomes.
Insights
Microplasmin treatment in rats after stroke showed mixed results. A 5 mg/kg dose reduced mortality and improved recovery, unlike a 10 mg/kg dose which worsened outcomes.
Area of Science:
- Neuroscience
- Pharmacology
- Stroke Research
Background:
- Middle cerebral artery occlusion (MCAO) is a common cause of ischemic stroke.
- Microplasmin is being investigated for potential neuroprotective and thrombolytic effects.
Purpose of the Study:
- To evaluate the impact of microplasmin on behavioral recovery and infarct volume following MCAO in a rat model.
- To determine dose-dependent effects of microplasmin on stroke outcomes.
Main Methods:
- Eighty rats underwent MCAO and were randomized into three groups: 5 mg/kg microplasmin, 10 mg/kg microplasmin, or saline control.
- Microplasmin was administered as a bolus followed by continuous infusion.
- Behavioral performance was assessed using Montoya's staircase test over 7-14 days post-surgery.
Main Results:
- No significant differences in infarct volume were observed across groups.
- Mortality was significantly lower in the 5 mg/kg microplasmin group compared to the 10 mg/kg group.
- The 5 mg/kg microplasmin group showed improved fine motor performance and body weight recovery compared to the 10 mg/kg group.
Conclusions:
- The 5 mg/kg microplasmin dose demonstrated a potential benefit by reducing mortality and enhancing behavioral rehabilitation in surviving rats.
- The 10 mg/kg microplasmin dose appeared to worsen outcomes compared to the lower dose and saline control.
- Results suggest a narrow therapeutic window for microplasmin in MCAO models.
