Abstract:
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.
摘要:
缺血性中风在全球范围内是一个重大问题,没有神经保护药物可用。寻找神经保护剂的许多失败归因于未能从临床前模型转化为人类,这已经与严格的临床前中风研究指南作了斗争。这里,我们提出了一项临床前中风试验的事后分析,在容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进行,据此,在动物饲养设施中实施了计划外的变更。这些变化严重影响了卒中后体重,导致卒中后手术前体重的90.6%的典型体重发生变化。卒中后平均为手术前体重的80.5%。这些变化似乎也会影响中风后的血压,随着住房组间从215.4增加到240.3mmHg,和中风后的功能结果,在粘性标签测试中接触的延迟增加了38%。这些数据突出了在使用生理或行为测量作为主要结果时严格控制住房条件的重要性。