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Monofilament intraluminal middle cerebral artery occlusion in the mouse
W M Clark1, N S Lessov, M P Dixon
1Oregon Stroke Center, Portland, USA.
Abstract:
The rat middle cerebral artery (MCA) occlusion model with an intraluminal filament is well characterized with a two hour period of occlusion in widespread use. The recent availability of transgenic animals has led to an interest in adapting the MCA model in the mouse. To date the model has not been well characterized in the mouse. We performed the present study to compare different durations of MCA occlusion and to validate new functional assessments in this model. The MCA occlusion model (5-0 filament) was used. Swiss-Webster mice, 24-44 g, were randomly assigned to four groups: one hour of occlusion; two hours of occlusion; three hours of occlusion; or permanent occlusion. At 48 hours post-ischemia, the animals were rated on three neurologic function scales, and then the brains were removed for lesion size determination. Overall, there was a significant difference in lesion volume (p < 0.001) between the groups. In the permanent group of mice, the average lesion volume was 78.41 +/- 17.47 mm (n = 12); two and three hours of ischemia produced 51.29 +/- 29.82 mm3 (n = 11) and 54.85 mm3 (n = 13), respectively, significantly different than the one hour group 14.84 +/- 31.34 mm3 (n = 11). All three functional scoring systems found significant overall differences between the four groups with our detailed General and Focal scores producing more robust between group treatment differences and showing correlation coefficients of r = 0.766 and r = 0.788, respectively to infarct volume. The MCA filament occlusion model can be successfully adapted in the mouse with either two or three hour occlusions producing reliable infarcts. New functional scoring systems unique to the mouse appear to add additional information.
Insights
This study successfully adapted the middle cerebral artery (MCA) occlusion model in mice, finding that two or three hours of occlusion reliably produce infarcts. New functional scoring systems also improved data interpretation for stroke research.
Area of Science:
- Neuroscience
- Stroke Research
- Animal Models
Background:
- The rat middle cerebral artery (MCA) occlusion model is widely used but not well-characterized in mice.
- Transgenic mouse availability necessitates adapting MCA occlusion models for research.
Purpose of the Study:
- To characterize the mouse MCA occlusion model using varying occlusion durations.
- To validate novel functional assessments for use in mouse stroke models.
Main Methods:
- Swiss-Webster mice underwent MCA occlusion for 1, 2, 3 hours, or permanently.
- Neurologic function was assessed using three scales 48 hours post-ischemia.
- Brain lesion volumes were determined and correlated with functional scores.
Main Results:
- Significant differences in lesion volume were observed across occlusion groups (p < 0.001).
- Two and three-hour occlusions produced significantly larger infarcts than one-hour occlusion.
- Novel general and focal scoring systems showed robust differences and correlated well with infarct volume (r=0.766, r=0.788).
Conclusions:
- The MCA filament occlusion model is adaptable to mice, with 2-3 hour occlusions yielding reliable infarcts.
- New mouse-specific functional scoring systems enhance data interpretation in stroke research.