Improving Large Animal Ischemic Stroke Models for Translational Studies in the Era of Recanalization

Abstract

Recanalization therapy with endovascular procedures has led to significant advances in the treatment of acute ischemic stroke. Animal models have been the basis for enhancing the development of novel treatments and therapeutic modalities. However, previous translational failures led to an increasing consensus that large animals should be included to bridge the gap between rodent and human studies. In the era of large vessel recanalization, large animal ischemic stroke models should be optimized for preclinical and translational stroke studies. Here we highlight recent progress of reproducing ischemic and reperfusion mechanisms in large animal models of stroke through surgical and endovascular methods. The importance of optimizing large animal stroke modeling is suggested by evaluating new findings from clinical trials and preclinical experiments using large animals, such as adopting advanced imaging analysis and long-term functional evaluation. Furthermore, we also acknowledge the importance of adhering to the Stroke Treatment and Academic Roundtable recommendations and the "3 R" principles to improve the quality and validity of large animal experiments. Large animal models offer many translational benefits; however, more work is still needed to enhance studies using large animal model on acute ischemic stroke in the era of recanalization.

Keywords: endovascular procedures; ischemia; magnetic resonance imaging; neuroprotection; reperfusion; tissue-type plasminogen activator.