Rodent Stroke Model Guidelines for Preclinical Stroke Trials (1st Edition)

Abstract

Translational stroke research is a challenging task that needs long term team work of the stroke research community. Highly reproducible stroke models with excellent outcome consistence are essential for obtaining useful data from preclinical stroke trials as well as for improving inter-lab comparability. However, our review of literature shows that the infarct variation coefficient of commonly performed stroke models ranges from 5% to 200%. An overall improvement of the commonly used stroke models will further improve the quality for experimental stroke research as well as inter-lab comparability. Many factors play a significant role in causing outcome variation; however, they have not yet been adequately addressed in the Stroke Therapy Academic Industry Roundtable (STAIR) recommendations and the Good Laboratory Practice (GLP). These critical factors include selection of anesthetics, maintenance of animal physiological environment, stroke outcome observation, and model specific factors that affect success rate and variation. The authors have reviewed these major factors that have been reported to influence stroke model outcome, herewith, provide the first edition of stroke model guidelines so to initiate active discussion on this topic. We hope to reach a general agreement among stroke researchers in the near future with its successive updated versions.

Modeling Stroke in Mice - Middle Cerebral Artery Occlusion with the Filament Model

“…Nevertheless, this requires a thorough control of confounders. 22 Small differences in operation technique may account for different effects on the infarct. 23,24 Furthermore, due to variances in cerebral vascular anatomy, different mouse strains show a different outcome.…”

Bilateral Common Carotid Artery Occlusion as an Adequate Preconditioning Stimulus to Induce Early Ischemic Tolerance to Focal Cerebral Ischemia

“…Another crucial point is the filament length. Optimal filament lengths between 9-11 mm are reported 15 . Due to the fact that our incisions were made proximal to the CCA bifurcation, we used a monofilament length of 13 mm and a thickness of approximately 200 μm.…”

“…For consistent results, duration of anesthesia and surgical procedures as well as other variables such as animal weights, brain temperatures during surgery, postsurgical fluid replenishment, postsurgical pain management as well as pre-and postsurgical cage enrichment should be standardized 15 . Particular attention requires maintenance of normothermic conditions of the mice throughout the complete period of anesthesia because hypothermia itself has a preconditioning effect and can therefore interfere with the BCCAO effect 16 .…”

Induction of Ischemic Stroke and Ischemia-reperfusion in Mice Using the Middle Artery Occlusion Technique and Visualization of Infarct Area

“…The success rate of the method described, as obtained by our group and reported by others, is of around 80 -90%. Nevertheless, several factors can influence the survival, including body temperature control and suture selection 20,21,22 . The maintenance of animal body temperature during surgery is important to improve animal survival.…”