临床前中风模型住房的计划外变化导致生理和行为数据结果的差异:事后分析。

Brain and neuroscience advances Pub Date : 2024-03-20 eCollection Date: 2024-01-01 DOI:10.1177/23982128241238934
Aisling McFall, Delyth Graham, Stuart A Nicklin, Lorraine M Work
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引用次数: 0

摘要

缺血性中风是全球面临的一个重大问题,目前尚无神经保护药物。在寻找神经保护剂的过程中,许多失败都归因于未能从临床前模型转化到人体,而严格的临床前中风研究指南已经解决了这一问题。在此,我们对一项临床前中风试验进行了事后分析,该试验是在易中风的自发性高血压大鼠中使用腔内丝状瞬时大脑中动脉闭塞进行的。这些变化严重影响了中风后的体重,导致体重从中风后手术前体重的 90.6% 降至中风后手术前体重的平均 80.5%。这些变化似乎还影响了中风后的血压(住房组之间的血压从 215.4 mmHg 上升到 240.3 mmHg)和中风后的功能结果(粘贴标签测试中的接触潜伏期增加了 38%)。这些数据强调了在使用生理或行为测量作为主要结果时严格控制饲养条件的重要性。
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Unscheduled changes in pre-clinical stroke model housing contributes to variance in physiological and behavioural data outcomes: A post hoc analysis.

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.

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