McFall Aisling, Graham Delyth, Nicklin Stuart A, Work Lorraine M
School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, UK.
Brain Neurosci Adv. 2024 Mar 20;8:23982128241238934. doi: 10.1177/23982128241238934. eCollection 2024 Jan-Dec.
Ischaemic stroke presents a significant problem worldwide with no neuroprotective drugs available. Many of the failures in the search for neuroprotectants are attributed to failure to translate from pre-clinical models to humans, which has been combatted with rigorous pre-clinical stroke research guidelines. Here, we present post hoc analysis of a pre-clinical stroke trial, conducted using intraluminal filament transient middle cerebral artery occlusion in the stroke-prone spontaneously hypertensive rat, whereby unscheduled changes were implemented in the animal housing facility. These changes severely impacted body weight post-stroke resulting in a change from the typical body weight of 90.6% of pre-surgery weight post-stroke, to on average 80.5% of pre-surgery weight post-stroke. The changes also appeared to impact post-stroke blood pressure, with an increase from 215.4 to 240.3 mmHg between housing groups, and functional outcome post-stroke, with a 38% increased latency to contact in the sticky label test. These data highlight the importance of tightly controlled housing conditions when using physiological or behavioural measurements as a primary outcome.
缺血性中风在全球范围内是一个重大问题，目前尚无神经保护药物。寻找神经保护剂的许多失败案例都归因于无法从临床前模型转化到人体，而这一问题已通过严格的临床前中风研究指南加以应对。在此，我们对一项临床前中风试验进行事后分析，该试验在易中风的自发性高血压大鼠中使用管腔内细丝短暂性大脑中动脉闭塞法进行，在此期间动物饲养设施发生了意外变化。这些变化严重影响了中风后的体重，导致中风后体重从典型的术前体重的90.6%，变为平均为术前体重的80.5%。这些变化似乎还影响了中风后的血压，不同饲养组之间血压从215.4 mmHg升高到240.3 mmHg，以及中风后的功能结局，在粘性标签测试中接触延迟增加了38%。这些数据凸显了在将生理或行为测量作为主要结局时，严格控制饲养条件的重要性。
