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建立一种评估 Circle Willis 穿孔小鼠模型蛛网膜下腔出血严重程度的新方案。

Establishment of a novel protocol for assessing the severity of subarachnoid hemorrhage in circle Willis perforation mouse model.

机构信息

Department of Neurosurgery, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University Dusseldorf, Mooren Str. 5, 40225, Dusseldorf, Germany.

Department of Neurosurgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

出版信息

Sci Rep. 2024 May 2;14(1):10147. doi: 10.1038/s41598-024-60237-w.

DOI:10.1038/s41598-024-60237-w
PMID:38698100
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11066000/
Abstract

The Circle of Willis perforation (cWp) mouse model is a key tool in subarachnoid hemorrhage (SAH) research; however, inconsistent bleeding volumes can challenge experimental reliability. To address this issue, we introduced the ROB Scoring System, a novel protocol integrating Rotarod Tests (RT), Open-field Tests (OT) video analysis, and daily Body Weight Loss (BWL) monitoring to precisely categorize SAH severity. Forty C57BL/6 mice underwent cWp SAH induction, categorized by ROB into severity subgroups (severe, moderate, mild). Validation compared ROB trends in subgroups, and ROB outcomes with autopsy results on postoperative days three and seven for acute and sub-acute evaluations. Mortality rates were analyzed via the survival log-rank test, revealing a significant difference among SAH subgroups (P < 0.05). Strong correlations between ROB grades and autopsy findings underscored its precision. Notably, the severe group exhibited 100% mortality within 4 days post SAH onset. Single parameters (RT, OT, BWL) were insufficient for distinguishing SAH severity levels. The ROB score represents a significant advancement, offering an objective method for precise categorization and addressing inherent bleeding variations in the cWp SAH model. This standardized protocol enhances the reliability and effectiveness of the SAH translational research, providing a valuable tool for future investigations into this critical area.

摘要

Willis 环穿孔(cWp)小鼠模型是蛛网膜下腔出血(SAH)研究的重要工具;然而,不一致的出血量可能会影响实验的可靠性。为了解决这个问题,我们引入了 ROB 评分系统,这是一种新的方案,结合了转棒测试(RT)、旷场测试(OT)视频分析和每日体重损失(BWL)监测,以精确分类 SAH 的严重程度。40 只 C57BL/6 小鼠接受了 cWp SAH 诱导,根据 ROB 分为严重、中度和轻度三个严重程度亚组。通过术后第 3 天和第 7 天的急性和亚急性评估,对 ROB 趋势在亚组中的验证、ROB 结果与尸检结果进行了比较。采用生存对数秩检验分析死亡率,结果表明 SAH 亚组之间存在显著差异(P<0.05)。ROB 分级与尸检结果之间存在很强的相关性,突出了其精确性。值得注意的是,严重组在 SAH 发作后 4 天内死亡率达到 100%。单一参数(RT、OT、BWL)不足以区分 SAH 的严重程度。ROB 评分是一个重大进展,为精确分类提供了一种客观方法,并解决了 cWp SAH 模型中固有的出血变化。这种标准化方案提高了 SAH 转化研究的可靠性和有效性,为该关键领域的未来研究提供了有价值的工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1de/11066000/86e680578d4c/41598_2024_60237_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1de/11066000/edea058cfa09/41598_2024_60237_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1de/11066000/35626a9fb37b/41598_2024_60237_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1de/11066000/86e680578d4c/41598_2024_60237_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1de/11066000/edea058cfa09/41598_2024_60237_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1de/11066000/35626a9fb37b/41598_2024_60237_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1de/11066000/86e680578d4c/41598_2024_60237_Fig3_HTML.jpg

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Endovascular Perforation Model for Subarachnoid Hemorrhage Combined with Magnetic Resonance Imaging (MRI).蛛网膜下腔出血合并磁共振成像(MRI)的血管内穿孔模型。
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The ESAS-score: A histological severity grading system of subarachnoid hemorrhage using the modified double hemorrhage model in rats.ESAS 评分:一种使用改良大鼠二次出血模型的蛛网膜下腔出血组织学严重程度分级系统。
PLoS One. 2020 Feb 25;15(2):e0227349. doi: 10.1371/journal.pone.0227349. eCollection 2020.
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