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Middle cerebral artery occlusion in rats: a neurological and pathological evaluation of a reproducible model
S A Menzies1, J T Hoff, A L Betz
1Department of Surgery, University of Michigan, Ann Arbor.
Abstract:
Middle cerebral artery occlusion (MCAO) in rats produces an infarct of varying size. We examined three factors that may influence this variability: animal weight, vascular anatomy, and extent of occlusion in rats undergoing MCAO. We also developed a four-point neurological evaluation scale and validated its usefulness by comparing it with a four-grade pathological determination of the size of the infarct. Of 82 animals subjected to a standard MCAO, 34 developed small cortical infarcts (pathological grades I-II; infarct size less than 25 mm2, 6-17% of the ipsilateral cortex surface area), and 48 large infarcts (pathological grades III-IV, infarct size greater than 25 mm2, 20-56% of surface area). We were able to predict the size of infarction from the neurological evaluation in 83% of the animals, and this accuracy reached 91% when grades I and II and III and IV were considered together (P less than 0.001). In 41 animals subjected to a more extensive vascular occlusion, 89% exhibited large infarcts. Four vascular patterns were identified but none played a significant role in the incidence or size of the cortical stroke. However, rats weighing less than 300 g showed a smaller lesion size than did rats greater than 300 g. Our proposed new MCAO technique appears useful in reproducing large-sized infarcts of the frontoparietal cortex.
Insights
This study investigated factors influencing stroke size in rats after middle cerebral artery occlusion (MCAO). A new neurological scale accurately predicted infarct size, aiding research into stroke variability.
Area of Science:
- Neuroscience
- Stroke Research
- Animal Models
Background:
- Middle cerebral artery occlusion (MCAO) in rats is a common model for studying ischemic stroke.
- Variability in infarct size is a significant challenge in MCAO research.
- Understanding factors influencing infarct size is crucial for reliable stroke modeling.
Purpose of the Study:
- To identify factors contributing to infarct size variability in rats undergoing MCAO.
- To develop and validate a neurological evaluation scale for predicting infarct size.
- To assess the impact of animal weight, vascular anatomy, and occlusion extent on stroke outcomes.
Main Methods:
- Standardized MCAO procedure in 82 rats.
- Development and validation of a four-point neurological evaluation scale against pathological infarct grading.
- Analysis of infarct size in relation to animal weight, vascular patterns, and occlusion extent.
- Comparison of infarct sizes between rats weighing <300g and >300g.
Main Results:
- A four-point neurological scale predicted infarct size with 83% accuracy (91% when combining grades).
- More extensive vascular occlusion led to large infarcts in 89% of animals.
- Rats weighing <300g exhibited smaller lesion sizes compared to heavier rats.
- Identified four vascular patterns, none significantly impacting stroke incidence or size.
Conclusions:
- The developed neurological scale is a reliable tool for predicting infarct size in MCAO models.
- Animal weight is a factor influencing infarct size, with lighter rats showing smaller lesions.
- The study highlights a reproducible MCAO technique for generating large frontoparietal cortex infarcts.