A Preclinical Systematic Review and Meta-Analysis of Behavior Testing in Mice Models of Ischemic Stroke

Stroke remains one of the most important causes of death and disability. Preclinical research is a powerful tool for understanding the molecular and cellular response to stroke. However, a lack of standardization in animal evaluation does not always ensure reproducible results. In the present study, we wanted to identify the best strategy for evaluating animal behavior post-experimental stroke. As such, a meta-analysis was made, evaluating behavioral tests done on male C57BL/6 mice subjected to stroke or sham surgery. Overall, fifty-six studies were included. Our results suggest that different types of tests should be used depending on the post-stroke period one needs to analyze. In the hyper-acute, post-stroke period, the best quantifier will be animal examination scoring, as it is a fast and inexpensive way to identify differences between groups. When evaluating stoke mice in the acute phase, a mix of animal examination and motor tests that focus on movement asymmetry (foot-fault and cylinder testing) seem to have the best chance of picking up differences between groups. Complex tasks (the rotarod test and Morris water maze) should be used within the chronic phase to evaluate differences between the late-subacute and chronic phases.