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小鼠实验性蛛网膜下腔出血模型的优化与评估

Optimization and evaluation of an experimental subarachnoid hemorrhage model in mice.

作者信息

Xiang Chao, Liu Fangming, Liu Boliang, Guo Wei, Wu Haitao, Hou Fandi, Zheng Zhanqiang, Chen Zhongcan, Suo Lina, Feng Guang, Ye Lisha, Wang Guohua, Gu Jianjun

机构信息

Department of Neurosurgery, Henan Provincial People's Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China.

Special Environmental Medicine and Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China.

出版信息

Sci Rep. 2025 May 26;15(1):18285. doi: 10.1038/s41598-025-03016-5.

DOI:10.1038/s41598-025-03016-5
PMID:40415031
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12104485/
Abstract

Subarachnoid hemorrhage (SAH) occurs when blood enters the subarachnoid space, typically due to aneurysm rupture, triggering complex pathophysiological processes. A reliable animal model is crucial for simulating SAH and investigating mechanisms of brain white matter injury. SAH was induced in C57BL/6J mice using an intraluminal perforation technique. Various filaments were tested to determine the optimal one, and filament depth was carefully measured. Postoperative evaluations included monitoring body weight, blood distribution on the skull, and clot formation. Cerebral blood flow was assessed, and neurological function was evaluated using modified Garcia scores, open field tests, and gait analysis. Myelin integrity was assessed by Luxol fast blue staining, and immunofluorescence was used to examine myelin, microglia, and neuronal integrity in the cortex and striatum. Using 4 - 0 polypropylene filaments advanced to 13 ± 1 mm at a 15-20 degree, we established a stable SAH mouse model with a success rate of 91.43% and a mortality rate of 6.25%. The SAH group showed motor impairments at 48 h post-surgery, along with myelin damage in the corpus callosum and striatum, oligodendrocyte damage, and neuronal injury.Our improved intraluminal perforation technique offers a stable and standardized SAH model, providing a reliable platform for studying SAH pathophysiology and testing new therapies.

摘要

蛛网膜下腔出血(SAH)是指血液进入蛛网膜下腔,通常是由于动脉瘤破裂引起的,会引发复杂的病理生理过程。一个可靠的动物模型对于模拟SAH和研究脑白质损伤机制至关重要。采用腔内穿孔技术在C57BL/6J小鼠中诱导SAH。测试了各种细丝以确定最佳细丝,并仔细测量了细丝深度。术后评估包括监测体重、颅骨上的血液分布和血凝块形成。评估脑血流量,并使用改良的加西亚评分、旷场试验和步态分析来评估神经功能。通过Luxol固蓝染色评估髓鞘完整性,并使用免疫荧光检查皮质和纹状体中的髓鞘、小胶质细胞和神经元完整性。使用4-0聚丙烯细丝以15-20度推进到13±1毫米,我们建立了一个稳定的SAH小鼠模型,成功率为91.43%,死亡率为6.25%。SAH组在术后48小时出现运动障碍,同时胼胝体和纹状体出现髓鞘损伤、少突胶质细胞损伤和神经元损伤。我们改进的腔内穿孔技术提供了一个稳定且标准化的SAH模型,为研究SAH病理生理学和测试新疗法提供了一个可靠的平台。

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本文引用的文献

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Confirming Subarachnoid Hemorrhage Induction in the Endovascular Puncture Mouse Model.确认血管内穿刺小鼠模型中的蛛网膜下腔出血诱导情况。
Brain Hemorrhages. 2022 Sep;3(3):111-116. doi: 10.1016/j.hest.2022.02.001. Epub 2022 Feb 18.
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Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021.全球、区域和国家层面蛛网膜下腔出血的流行病学趋势:1990 年至 2021 年的趋势分析研究。
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Development of a 3D Brain Model to Study Sex-Specific Neuroinflammation After Hemorrhagic Stroke.
用于研究出血性中风后性别特异性神经炎症的3D脑模型的开发。
Transl Stroke Res. 2025 Jun;16(3):655-671. doi: 10.1007/s12975-024-01243-y. Epub 2024 Apr 1.
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The role of early cerebral edema and hematoma assessment in aneurysmal subarachnoid hemorrhage (a-SAH) in predicting early brain injury (EBI) and cognitive impairment: a case controlled study.早期脑水肿和血肿评估在预测动脉瘤性蛛网膜下腔出血(a-SAH)中的早期脑损伤(EBI)和认知障碍中的作用:一项病例对照研究。
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Red Blood Cells in the Cerebrospinal Fluid Compartment After Subarachnoid Haemorrhage: Significance and Emerging Therapeutic Strategies.蛛网膜下腔出血后脑脊液腔室中的红细胞:意义及新兴治疗策略
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Simple procedure for assessing diffuse subarachnoid hemorrhage successfully created using filament perforation method in mice.利用纤维穿孔法在小鼠中成功创建了一种用于评估弥漫性蛛网膜下腔出血的简单方法。
Animal Model Exp Med. 2024 Feb;7(1):77-81. doi: 10.1002/ame2.12372. Epub 2023 Dec 19.
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Fluids Barriers CNS. 2023 Dec 6;20(1):91. doi: 10.1186/s12987-023-00486-5.
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