Review: Preclinical Models of Large-Vessel Occlusion Stroke

Preclinical models of large-vessel occlusion (LVO) stroke play an important role in testing novel thrombolytic and neuroprotective agents, as well as assessing endovascular devices for endovascular thrombectomy. Depending on the modality used to model LVO stroke, different aspects of human stroke pathophysiology can be recapitulated. Thus, variables including size and region of the occlusion, composition of the clot, and degree of reperfusion can be controlled. We conducted a thorough literature review of all the preclinical models of stroke used currently. We searched for studies using the PubMed database and included original studies, reviews, systematic reviews, and meta-analyses. In this review, we describe the considerations in choosing a preclinical model of LVO stroke. We provide an overview of available small- and large-animal LVO stroke models that can be used in stroke research as well as the benefits and limitations of each. We then discuss the current outcome measures that can be evaluated through these models, in terms of both tissue damage and behavioral outcome. We also discuss the advantages and disadvantages of each animal model. Finally, based on this summary, we propose that mice represent the most versatile small-animal LVO model and dogs are the most appropriate large-animal LVO stroke model to translate candidate drugs and devices into clinical trials.