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A mouse model of embolic focal cerebral ischemia
1Department of Neurology, Henry Ford Health Science Center, Detroit, Michigan 48202, U.S.A.
Abstract:
We developed a mouse model of embolic focal cerebral ischemia, in which a fibrin-rich clot was placed at the origin of the middle cerebral artery (MCA) in C57BL/6J mice (n = 31) and B6C3 mice (n = 10). An additional three non-embolized C57BL/6J mice were used as a control. Embolus induction, cerebral vascular perfusion deficit, and consequent ischemic cell damage were confirmed by histopathology, immunohistochemistry, laser confocal microscopy, and regional cerebral blood flow (rCBF) measurements. Reduction in rCBF and cerebral infarct were not detected in the control animals. An embolus was found in all C57BL/6J and B6C3 mice at 24 hours after injection of a clot. Regional CBF in the ipsilateral parietal cortex decreased to 23% (P < 0.05) and 17% (P < 0.05) of preembolization levels immediately and persisted for at least 1 hour in C57BL/6J mice (n = 6) and in B6C3 mice (n = 3), respectively. A significant decrease of rCBF was accompanied by a corresponding reduction of plasma perfusion in the ipsilateral MCA territory. Neurons exhibited marked reduction in microtubule-associated protein-2 immunostaining coincident with the area of perfusion deficit. The percent infarct volume was 30.3% +/- 13.4% for C57BL/6J mice (n = 17), and 38.3% +/- 15.3% for B6C3 mice (n = 7) at 24 hours after embolization. This model of embolic ischemia is relevant to thromboembolic stroke in humans and may be useful to investigate embolic cerebral ischemia in the genetically altered mouse and for evaluation of antiembolic therapies.
Insights
Researchers created a mouse model for embolic stroke, mimicking human thromboembolic events. This model accurately replicates cerebral ischemia and infarct, proving useful for studying stroke and testing new therapies.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Animal Models
Background:
- Embolic focal cerebral ischemia is a significant cause of stroke in humans.
- Developing accurate animal models is crucial for understanding stroke pathophysiology and evaluating therapeutic interventions.
Purpose of the Study:
- To develop and validate a mouse model of embolic focal cerebral ischemia.
- To assess the utility of this model for studying cerebral ischemia and evaluating antiembolic therapies.
Main Methods:
- Induction of embolic focal cerebral ischemia by placing a fibrin-rich clot in the middle cerebral artery (MCA) of C57BL/6J and B6C3 mice.
- Confirmation of embolus, perfusion deficit, and cell damage using histopathology, immunohistochemistry, laser confocal microscopy, and regional cerebral blood flow (rCBF) measurements.
- Quantification of infarct volume at 24 hours post-embolization.
Main Results:
- The developed model successfully induced embolic ischemia, confirmed by embolus presence and significant reduction in rCBF (23-17%) in the ipsilateral parietal cortex.
- Cerebral infarct volumes were substantial (30.3% in C57BL/6J, 38.3% in B6C3 mice) at 24 hours post-embolization.
- Control animals showed no reduction in rCBF or cerebral infarct, validating the model's specificity.
Conclusions:
- The established mouse model accurately replicates key features of human embolic stroke, including perfusion deficits and infarct formation.
- This model is a valuable tool for investigating the mechanisms of embolic cerebral ischemia.
- The model provides a platform for the preclinical evaluation of novel antiembolic therapies.