Turner Ryan C, DiPasquale Kenneth, Logsdon Aric F, Tan Zhenjun, Naser Zachary J, Huber Jason D, Rosen Charles L, Lucke-Wold Brandon P
Department of Neurosurgery, School of Medicine, West Virginia University, Morgantown, West Virginia 26506, USA; Center for Neuroscience, School of Medicine, West Virginia University, Morgantown, West Virginia 26506, USA.
Center for Neuroscience, School of Medicine, West Virginia University, Morgantown, West Virginia 26506, USA; Department of Basic Pharmaceutical Sciences, School of Pharmacy, West Virginia University, Morgantown, West Virginia 26506, USA.
J Syst Integr Neurosci. 2016 Dec;2(4). doi: 10.15761/JSIN.1000136. Epub 2016 Oct 11.
The failed translation of proposed therapeutic agents for ischemic stroke from preclinical to clinical studies has led to increased scrutiny of preclinical studies, namely the model and outcome measures utilized. Preclinical studies routinely use infarct volume as an experimental endpoint or measure in studies employing young-adult, healthy male animals despite the fact that clinically, ischemic stroke is a disease of the elderly and improvements in functional outcome from pre- to post-intervention remains the most widely utilized assessment. The validity of infarct volume as a surrogate measure for functional outcome remains unclear in clinical studies as well as preclinical studies, particularly those utilizing a more clinically relevant aged thromboembolic model. In this work, we will address the relationship between acute and chronic functional outcome and infarct volume using a variety of functional assessments ranging from more simplistic, subjective measurements such as the modified Neurologic Severity Score (mNSS), to more complex, objective measurements such as grip strength and inclined plane.
缺血性中风治疗药物从临床前研究到临床研究的翻译失败，导致对临床前研究的审查增加，即所使用的模型和结果测量方法。临床前研究通常将梗死体积作为实验终点或测量指标，在使用年轻、健康雄性动物的研究中也是如此，尽管在临床上，缺血性中风是一种老年疾病，干预前后功能结果的改善仍然是最广泛使用的评估方法。梗死体积作为功能结果替代指标的有效性在临床研究和临床前研究中仍不明确，特别是那些使用更具临床相关性的老年血栓栓塞模型的研究。在这项工作中，我们将使用从更简单、主观的测量方法（如改良神经功能缺损评分（mNSS））到更复杂、客观的测量方法（如握力和斜面试验）等各种功能评估方法，来探讨急性和慢性功能结果与梗死体积之间的关系。
