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Updated: Jul 15, 2025
Surgical Approach for Middle Cerebral Artery Occlusion and Reperfusion Induced Stroke in Mice
Published on: October 20, 2016
Prediction of Stroke Outcome in Mice Based on Noninvasive MRI and Behavioral Testing
Felix Knab1,2, Stefan Paul Koch1,2,3, Sebastian Major1,2
1Charité Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Klinik und Hochschulambulanz für Neurologie, Department of Experimental Neurology, Germany (F.K., S.P.K., S. Major, T.D.F., S. Mueller, P.E., M. Eggers, M.T.C.K., J.W., D.B., S.K., J.P.D., A.M., M. Endres, U.D., N.W., C.J.H., P.B.-S., C.H.).
Background:
Prediction of poststroke outcome using the degree of subacute deficit or magnetic resonance imaging is well studied in humans. While mice are the most commonly used animals in preclinical stroke research, systematic analysis of outcome predictors is lacking.
Methods:
We intended to incorporate heterogeneity into our retrospective study to broaden the applicability of our findings and prediction tools. We therefore analyzed the effect of 30, 45, and 60 minutes of arterial occlusion on the variance of stroke volumes. Next, we built a heterogeneous cohort of 215 mice using data from 15 studies that included 45 minutes of middle cerebral artery occlusion and various genotypes. Motor function was measured using a modified protocol for the staircase test of skilled reaching. Phases of subacute and residual deficit were defined. Magnetic resonance images of stroke lesions were coregistered on the Allen Mouse Brain Atlas to characterize stroke topology. Different random forest prediction models that either used motor-functional deficit or imaging parameters were generated for the subacute and residual deficits.
Results:
Variance of stroke volumes was increased by 45 minutes of arterial occlusion compared with 60 minutes. The inclusion of various genotypes enhanced heterogeneity further. We detected both a subacute and residual motor-functional deficit after stroke in mice and different recovery trajectories could be observed. In mice with small cortical lesions, lesion volume was the best predictor of the subacute deficit. The residual deficit could be predicted most accurately by the degree of the subacute deficit. When using imaging parameters for the prediction of the residual deficit, including information about the lesion topology increased prediction accuracy. A subset of anatomic regions within the ischemic lesion had particular impact on the prediction of long-term outcomes. Prediction accuracy depended on the degree of functional impairment.
Conclusions:
For the first time, we developed and validated a robust tool for the prediction of functional outcomes after experimental stroke in mice using a large and genetically heterogeneous cohort. These results are discussed in light of study design and imaging limitations. In the future, using outcome prediction can improve the design of preclinical studies and guide intervention decisions.
Insights
This study developed a robust prediction tool for functional outcomes after experimental stroke in mice. The tool uses motor deficits and lesion imaging to improve preclinical research and intervention decisions.
Area of Science:
- Neuroscience
- Translational Medicine
- Preclinical Research
Background:
- Human stroke outcome prediction is established, but predictors in mice, the primary preclinical model, are understudied.
- Lack of systematic analysis hinders the translation of mouse stroke research findings to human therapies.
Purpose of the Study:
- To develop and validate a robust prediction tool for functional outcomes after experimental stroke in mice.
- To incorporate heterogeneity in mouse models to enhance the applicability of prediction tools.
Main Methods:
- Retrospective analysis of 215 mice from 15 studies with 45-minute middle cerebral artery occlusion and varied genotypes.
- Assessment of motor function using the staircase test and characterization of stroke lesions via MRI coregistered to the Allen Mouse Brain Atlas.
- Development of random forest models using motor-functional deficits and/or imaging parameters to predict subacute and residual deficits.
Main Results:
- Forty-five minutes of arterial occlusion increased stroke volume variance, with genotype further enhancing heterogeneity.
- Subacute deficit was best predicted by lesion volume in small cortical strokes; residual deficit was best predicted by the subacute deficit.
- Including lesion topology in imaging parameters improved residual deficit prediction accuracy, with specific anatomic regions showing particular impact.
Conclusions:
- A robust, validated tool for predicting functional outcomes in genetically heterogeneous mouse stroke models was developed.
- This tool can enhance preclinical study design and guide intervention strategies in stroke research.
- Findings highlight the importance of considering study design and imaging limitations in outcome prediction.
