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Embolic Middle Cerebral Artery Occlusion (MCAO) for Ischemic Stroke with Homologous Blood Clots in Rats
Published on: September 17, 2014
[Effect of recombinant microplasmin on acute cerebral infarction in rats]
Jie-ying Fu1, Jian-ping Ren, Li-bo Zou
1Institute of Radiation and Irradiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
Abstract:
The effect of recombinant microplasmin (micro-plasmin) on acute cerebral infarction was evaluated in rats, and compared with recombinant tissue plasminogen activator (rt-PA). After the model of middle cerebral artery occlusion (MCAO) was established by autologous blood clots, different doses of micro-plasmin (2.5, 5, and 10 mg x kg(-1)) were administered into the thrombus intra-arterial. Twelve hours after administration of micro-plasmin, the neurological deficit score of rats was recorded and the infarct volumes were determined. Bleeding time (BT), fibrin degradation product (FDP) concentration in serum and thrombin time (TT), prothrombin time (PT) and fibrinogen (FIB) concentration in plasma were tested after administration. Intra-arterial administration of micro-plasmin could reduce significantly neurological deficit score and infarct volumes in MCAO rats. FDP concentration increased significantly as compared with model group. There were no significant differences in TT, PT and BT. FIB concentration reduced markedly as compared with model group, but had no significant difference as compared with sham group. The results suggest that micro-plasmin is effective in treatment of rat acute cerebral infarction, and has no significant influence on fibrinolytic system and blood clotting system, indicating that micro-plasmin may be useful for treatment of acute cerebral infarction, and not lead to hemorrhage. Micro-plasmin seems to be distinguished from clinical used rt-PA by its no hemorrhage effect.
Insights
Recombinant microplasmin effectively treats acute cerebral infarction in rats by reducing infarct volume and neurological deficits. Unlike rt-PA, microplasmin shows no significant impact on bleeding or clotting systems, suggesting a safer therapeutic profile.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Acute cerebral infarction, or stroke, is a leading cause of death and disability.
- Recombinant tissue plasminogen activator (rt-PA) is a common treatment but carries risks of hemorrhage.
- Novel therapeutic agents are needed to improve stroke treatment outcomes.
Purpose of the Study:
- To evaluate the efficacy and safety of recombinant microplasmin in a rat model of acute cerebral infarction.
- To compare the effects of microplasmin with rt-PA regarding neurological deficits, infarct volume, and hemostatic parameters.
Main Methods:
- A middle cerebral artery occlusion (MCAO) model was established in rats using autologous blood clots.
- Different doses of microplasmin were administered intra-arterially into the thrombus.
- Neurological deficit scores, infarct volumes, bleeding time, and coagulation parameters (TT, PT, FIB, FDP) were assessed.
Main Results:
- Microplasmin significantly reduced neurological deficit scores and infarct volumes in MCAO rats.
- Fibrin degradation product (FDP) levels increased significantly, indicating fibrinolytic activity.
- No significant changes were observed in thrombin time (TT), prothrombin time (PT), or bleeding time (BT).
- Fibrinogen (FIB) levels decreased but remained comparable to the sham group.
Conclusions:
- Recombinant microplasmin is effective in treating acute cerebral infarction in rats.
- Microplasmin demonstrates a favorable safety profile with no significant influence on the fibrinolytic and blood clotting systems.
- Microplasmin may offer a safer alternative to rt-PA for stroke treatment due to its lack of hemorrhage-inducing effects.
