Comparison of Large Animal Models for Acute Ischemic Stroke: Which Model to Use?
Aladdin Taha1,2, Joaquim Bobi1, Ruben Dammers3
1Division of Experimental Cardiology, Department of Cardiology (A.T., J.B., D.J.D., H.M.M.v.B.), Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Abstract:
Translation of acute ischemic stroke research to the clinical setting remains limited over the last few decades with only one drug, recombinant tissue-type plasminogen activator, successfully completing the path from experimental study to clinical practice. To improve the selection of experimental treatments before testing in clinical studies, the use of large gyrencephalic animal models of acute ischemic stroke has been recommended. Currently, these models include, among others, dogs, swine, sheep, and nonhuman primates that closely emulate aspects of the human setting of brain ischemia and reperfusion. Species-specific characteristics, such as the cerebrovascular architecture or pathophysiology of thrombotic/ischemic processes, significantly influence the suitability of a model to address specific research questions. In this article, we review key characteristics of the main large animal models used in translational studies of acute ischemic stroke, regarding (1) anatomy and physiology of the cerebral vasculature, including brain morphology, coagulation characteristics, and immune function; (2) ischemic stroke modeling, including vessel occlusion approaches, reproducibility of infarct size, procedural complications, and functional outcome assessment; and (3) implementation aspects, including ethics, logistics, and costs. This review specifically aims to facilitate the selection of the appropriate large animal model for studies on acute ischemic stroke, based on specific research questions and large animal model characteristics.
Insights
Selecting the right large animal model is crucial for advancing acute ischemic stroke research. This review compares key features of models like dogs, swine, sheep, and nonhuman primates to aid researchers in choosing the best fit for their studies.
Area of Science:
- Neuroscience
- Translational Medicine
- Cardiovascular Research
Background:
- Translational research for acute ischemic stroke (AIS) has seen limited success, with few experimental treatments reaching clinical practice.
- Large gyrencephalic animal models are recommended to improve preclinical treatment selection for AIS.
- Existing models (dogs, swine, sheep, nonhuman primates) mimic human brain ischemia and reperfusion but have species-specific differences.
Purpose of the Study:
- To review and compare key characteristics of large animal models for translational AIS research.
- To guide the selection of appropriate animal models based on specific research questions.
- To provide a comprehensive overview of anatomical, physiological, modeling, and implementation aspects.
Main Methods:
- Review of literature on large gyrencephalic animal models for AIS.
- Analysis of species-specific cerebrovascular anatomy, physiology, and coagulation.
- Evaluation of ischemic stroke induction methods, infarct reproducibility, and outcome assessment.
- Consideration of ethical, logistical, and cost factors.
Main Results:
- Detailed comparison of canine, swine, ovine, and nonhuman primate models.
- Highlighting species-specific variations in cerebral vasculature, coagulation, and immune responses.
- Assessment of different vessel occlusion techniques and their impact on infarct size and reproducibility.
- Discussion of functional outcome measures and procedural complications.
Conclusions:
- The choice of large animal model significantly impacts the translatability of AIS research findings.
- Understanding species-specific characteristics is essential for designing robust preclinical studies.
- This review provides a framework for selecting optimal large animal models to advance AIS therapeutics.
