Division 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.
Department of Neurology, Stroke Center (A.T., D.W.J.D.), Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Stroke. 2022 Apr;53(4):1411-1422. doi: 10.1161/STROKEAHA.121.036050. Epub 2022 Feb 15.
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.
在过去的几十年里，将急性缺血性脑卒中研究转化为临床应用仍然受到限制，只有一种药物——重组组织型纤溶酶原激活剂成功地完成了从实验研究到临床实践的转化。为了提高在临床试验中测试之前选择实验性治疗方法的效果，建议使用大型脑回动物模型进行急性缺血性脑卒中研究。目前，这些模型包括狗、猪、绵羊和非人类灵长类动物等，它们在很大程度上模拟了人类脑缺血再灌注的情况。物种特异性特征，如脑血管结构或血栓形成/缺血过程的病理生理学，显著影响模型对特定研究问题的适用性。在本文中，我们回顾了急性缺血性脑卒中转化研究中主要大型动物模型的关键特征，包括（1）脑血管解剖学和生理学，包括脑形态、凝血特性和免疫功能；（2）缺血性脑卒中模型建立，包括血管闭塞方法、梗死面积的可重复性、程序并发症和功能结果评估；（3）实施方面，包括伦理学、后勤和成本。本综述的目的是根据特定的研究问题和大型动物模型的特征，为急性缺血性脑卒中研究选择合适的大型动物模型提供参考。
