Transient Middle Cerebral Artery Occlusion in Rats as a Nonclinical Model of Ischemic Stroke: A Systematic Review

Background: Ischemic stroke remains a leading cause of mortality and disability worldwide. Despite extensive preclinical research, most neuroprotective strategies have failed to translate into clinical benefit, partly due to methodological variability. The transient intraluminal filament middle cerebral artery occlusion (tifMCAO) model is widely used, yet its implementation lacks consistency. This review aimed to characterize tifMCAO methodologies in adult rats and examine how experimental variability relates to reported outcomes. Methods: A systematic review was conducted following PRISMA guidelines. Studies using tifMCAO in adult rats were included. MEDLINE (PubMed), Web of Science, and Scopus were searched up to March 2025. Risk of bias was assessed using the SYRCLE tool and reporting quality using the ARRIVE checklist. The protocol was registered in PROSPERO (CRD420251140869). Results were synthesized narratively. Results: A total of 125 studies were included. A commonly used framework involved male Sprague–Dawley rats (6–12 weeks), silicone-coated monofilaments, occlusion durations of 60–120 min (most frequently 90 min), and isoflurane anesthesia, although this reflects methodological convergence rather than true standardization. Substantial variability was observed across methodological parameters. Variations in ischemia duration, filament properties, and anesthesia were associated with differences in infarct size, blood–brain barrier disruption, and functional outcomes. Conclusions: The tifMCAO model shows partial methodological convergence alongside significant variability influencing outcomes. Improved standardization and reporting are essential to enhance reproducibility and translational relevance.