Method parameters' impact on mortality and variability in mouse stroke experiments: a meta-analysis.

Area of Science:

• Neuroscience
• Pharmacology
• Translational Medicine

Background:

• Thrombolysis is the sole pharmacological treatment for ischemic stroke, despite numerous drug failures in clinical trials.
• Preclinical study quality, particularly low statistical power, is implicated in the high failure rate of potential stroke therapies.
• Optimizing animal models for reduced mortality and outcome variability is essential for reliable preclinical research.

Purpose of the Study:

• To investigate the impact of methodological parameters on infarct size variability and mortality in experimental mouse stroke models.
• To provide guidance for researchers aiming to enhance the reproducibility and predictive value of preclinical stroke studies.
• To identify specific experimental conditions that minimize outcome variability and unnecessary animal loss.

Main Methods:

• A hypothesis-driven meta-analysis was conducted using data extracted from 334 published experimental mouse stroke articles.
• The study analyzed the influence of various methodological parameters on infarct size variability and mortality.
• Key parameters investigated included mouse strain, occlusion method, and surgical techniques.

Main Results:

• The use of Swiss and C57BL6 mice, combined with permanent middle cerebral artery occlusion, resulted in the lowest infarct size variability.
• Embolic stroke models were found to increase infarct size variability.
• Swiss mice exhibited higher mortality rates compared to other strains.

Conclusions:

• Specific mouse strains and permanent middle cerebral artery occlusion methods are recommended for reducing variability in preclinical stroke research.
• Researchers should carefully select experimental parameters to improve the reliability and efficiency of mouse stroke models.
• This meta-analysis provides critical data to guide the optimization of experimental designs, ultimately aiming to improve the translation of preclinical findings to clinical applications.