Comparison of Large Animal Models for Acute Ischemic Stroke: Which Model to Use?

Aladdin Taha, Joaquim Bobi, Ruben Dammers, Rick M. Dijkhuizen, Antje Y. Dreyer, Adriaan C.G.M. Van Es, Fabienne Ferrara, Matthew J. Gounis, Björn Nitzsche, Simon Platt, Michael H. Stoffel, Victor Volovici, Gregory J. Del Zoppo, Dirk J. Duncker, Diederik W.J. Dippel, Johannes Boltze, Heleen M.M. Van Beusekom*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1411-1422
Number of pages12
JournalStroke
Volume53
Issue number4
DOIs
Publication statusPublished - 1 Apr 2022

Bibliographical note

Funding Information:
We acknowledge the support of the Netherlands Cardiovascular Research Initiative, which is supported by the Dutch Heart Foundation (CVON2015-01: CONTRAST), the support of the Brain Foundation Netherlands (HA2015.01.06), and the support of Health~Holland, Top Sector Life Sciences & Health (LSHM17016), Medtronic, Cerenovus, and Stryker European Operations BV. The collaboration project is additionally financed by the Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships.

Funding Information:
We acknowledge the support of the Netherlands Cardiovascular Research Initiative, which is supported by the Dutch Heart Foundation (CVON2015-01: CONTRAST), the support of the Brain Foundation Netherlands (HA2015.01.06), and the support of Health-Holland, Top Sector Life Sciences & Health (LSHM17016), Medtronic, Cerenovus, and Stryker European Operations BV. The collaboration project is additionally financed by the Ministry of Economic Affairs by means of the PPP Allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships.

Funding Information:
Dr Gounis has been a consultant on a fee-per-hour basis for Astrocyte Pharmaceuticals, Cerenovus, Imperative Care, Medtronic Neurovascular, Mivi Neurosciences, Phenox, Q’Apel, Route 92 Medical, Stryker Neurovascular, and Wallaby Medical; holds stock in Galaxy Medical, Imperative Care, InNeuroCo, and Neurogami; and has received research support from the National Institutes of Health (NIH), the United States–Israel Binational Science Foundation, Anaconda, ApicBio, Arsenal Medical, Axovant, Cerenovus, Ceretrieve, Cook Medical, Galaxy Therapeutics, Gentuity, Imperative Care, InNeuroCo, Insera, Magneto, Microvention, Medtronic Neurovascular, MIVI Neurosciences, Naglreiter MDDO, Neurogami, Omniox, Philips Healthcare, Rapid Medical, Route 92 Medical, Stryker Neurovascular, Syntheon, ThrombX Medical, and the Wyss Institute. Dr Dippel reports funding from the Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organisation for Health Research and Development, and Health Holland Top Sector Life Sciences & Health and unrestricted grants from Penumbra, Inc, Stryker European Operations BV, Medtronic, Thrombolytic Science, LLC, and Cerenovus for research, all paid to institution. Dr Boltze has been a consultant for Astrocyte Pharmaceuticals. Dr van Beusekom reports funding from the Dutch Heart Foundation. The other authors report no conflicts.

Publisher Copyright:
© 2022 American Heart Association, Inc.

Fingerprint

Dive into the research topics of 'Comparison of Large Animal Models for Acute Ischemic Stroke: Which Model to Use?'. Together they form a unique fingerprint.

Cite this