García-Alfonso Enrique, Ramírez-Sánchez Jeney, Wong-Guerra Maylin, Fonseca-Fonseca Luis Arturo, Montano-Peguero Yanay, Risco-Acevedo Daniela, Núñez-Figueredo Yanier
Laboratory of Experimental Neuropharmacology, Center for Drug Research and Development (CIDEM), 26th Avenue 1605, Havana, 10600, Cuba.
Neuroprotection Lab, Pharmaceutical Division, Center for Genetic Engineering and Biotechnology (CIGB), 31st Avenue 15802, Havana, 11600, Cuba.
Pharmacol Rep. 2025 Jul 3. doi: 10.1007/s43440-025-00747-0.
Cerebrovascular diseases are highly lethal and disabling events. Stroke is most commonly modeled using focal ischemia, of which middle cerebral artery occlusion (MCAO) is widely employed. Reproducible and reliable animal models are crucial for studying the pathophysiology of diseases and the evaluation of therapeutic candidates. However, despite showing efficacy in experimental studies, neuroprotective approaches have failed to translate into clinical benefit so far. A key measure to improve preclinical stroke research is the inclusion of functional endpoints intended to cover a wide range of parameters. The selection of appropriate tests is a critical issue and a challenging task, given the many variables to be considered. These variables include the experimental species, strain, sex, age, occlusion method and duration, infarct size and location, and degree of collateral irrigation, operational costs, among others. The focus of this review is on the behavioral tests most commonly used to identify neurological alterations associated with sensorimotor deficits following transient cerebral ischemia in rats and mice. Commonly used tests include the neurological score, the adhesive removal test, the hanging wire test, the corner test, the cylinder test, and the rotarod test. Functional endpoints must be included in preclinical testing, including sensorimotor and cognitive function, given the variable recovery rates of specific neurological functions. Importantly, screening for sensorimotor function prior to cognitive testing ensures accurate conclusions and helps identify the best specific conditions with minimal confounding by neurological abnormalities. Behavioral outcomes allow assessment of the severity, persistence, or recovery of post-ischemic injury over time.
脑血管疾病是极具致死性和致残性的事件。中风最常通过局灶性缺血来建模,其中大脑中动脉闭塞(MCAO)被广泛应用。可重复且可靠的动物模型对于研究疾病的病理生理学和评估候选治疗方法至关重要。然而,尽管在实验研究中显示出疗效,但迄今为止神经保护方法尚未转化为临床益处。改善临床前中风研究的一项关键措施是纳入旨在涵盖广泛参数的功能终点。鉴于需要考虑众多变量,选择合适的测试是一个关键问题且具有挑战性。这些变量包括实验物种、品系、性别、年龄、闭塞方法和持续时间、梗死灶大小和位置、侧支灌注程度、运营成本等。本综述的重点是最常用于识别大鼠和小鼠短暂性脑缺血后与感觉运动缺陷相关的神经学改变的行为测试。常用测试包括神经学评分、黏附去除测试、悬线测试、转角测试、圆筒测试和转棒测试。鉴于特定神经功能的恢复率各不相同,功能终点必须纳入临床前测试,包括感觉运动和认知功能。重要的是,在进行认知测试之前先筛查感觉运动功能可确保得出准确结论,并有助于在神经异常造成的混淆最小的情况下确定最佳的具体条件。行为结果可用于评估缺血性损伤随时间的严重程度、持续时间或恢复情况。