title: Method parameters' impact on mortality and variability in mouse stroke experiments: a meta-analysis.
abstract: Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specific pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible. As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters' impact on infarct size variability and mortality. The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality. Our study offers guidance for researchers striving to optimize mouse stroke models.
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Sweden.
authors.forename: Edvin
authors.initials: E
authors.lastname: Ingberg
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Sweden.
authors.forename: Hua
authors.initials: H
authors.lastname: Dock
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Sweden.
authors.forename: Elvar
authors.initials: E
authors.lastname: Theodorsson
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Sweden.|Division of Neuro and Inflammation Science, Department of Clinical and Experimental Medicine, Linköping University, Department of Neurosurgery, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland, Sweden.
authors.forename: Annette
authors.initials: A
authors.lastname: Theodorsson
authors.affiliation: Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Sweden.|Vårdvetenskapligt Forskningscentrum/Centre for Health Sciences, Örebro University Hospital, County Council of Örebro, Örebro, Sweden.|School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: Jakob O
authors.initials: JO
authors.lastname: Ström
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000401:mortality* / Q000473:pathology; D051379:Mice; D020768:Middle Cerebral Artery / Q000503:physiopathology*; D020521:Stroke / Q000401:mortality* / Q000503:physiopathology