Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, Grafton, MA 01536, USA.
Rev Neurosci. 2018 Aug 28;29(6):661-674. doi: 10.1515/revneuro-2017-0076.
Rodent and rabbit stroke models have been instrumental in our current understanding of stroke pathophysiology; however, translational failure is a significant problem in preclinical ischemic stroke research today. There are a number of different focal cerebral ischemia models that vary in their utility, pathophysiology of causing disease, and their response to treatments. Unfortunately, despite active preclinical research using these models, treatment options for ischemic stroke have not significantly advanced since the food and drug administration approval of tissue plasminogen activator in 1996. This review aims to summarize current stroke therapies, the preclinical experimental models used to help develop stroke therapies, as well as their advantages and limitations. In addition, this review discusses the potential for naturally occurring canine ischemic stroke models to compliment current preclinical models and to help bridge the translational gap between small mammal models and human clinical trials.
啮齿动物和兔卒中模型在我们目前对卒中病理生理学的理解中发挥了重要作用;然而,转化失败是当今临床前缺血性卒中研究中的一个重大问题。有许多不同的局灶性脑缺血模型,它们在用途、引起疾病的病理生理学以及对治疗的反应方面有所不同。不幸的是,尽管使用这些模型进行了积极的临床前研究,但自 1996 年食品和药物管理局批准组织型纤溶酶原激活物以来,缺血性卒中的治疗选择并没有显著进展。本综述旨在总结目前的卒中治疗方法、用于帮助开发卒中治疗方法的临床前实验模型,以及它们的优缺点。此外,本综述还讨论了自然发生的犬缺血性卒中模型补充当前临床前模型的潜力,并有助于缩小小型哺乳动物模型与人类临床试验之间的转化差距。