Laboratory Animal and Comparative Medicine ›› 2022, Vol. 42 ›› Issue (1): 54-61.DOI: 10.12300/j.issn.1674-5817.2021.049
• Animal Models of Human Diseases • Previous Articles Next Articles
Bo DONG1(), Jiaxin LIU1(
), Wei XIONG2, Songqi TANG2, Wei HUANG1(
)
Received:
2021-03-09
Revised:
2021-09-06
Online:
2022-02-25
Published:
2022-02-25
Contact:
Wei HUANG
CLC Number:
Bo DONG,Jiaxin LIU,Wei XIONG,et al. Progress in Animal Models of Ischemic Stroke[J]. Laboratory Animal and Comparative Medicine, 2022, 42(1): 54-61. DOI: 10.12300/j.issn.1674-5817.2021.049.
Add to citation manager EndNote|Ris|BibTeX
URL: https://www.slarc.org.cn/dwyx/EN/10.12300/j.issn.1674-5817.2021.049
造模方法 | 模型动物 | 评价指标 |
---|---|---|
线栓法 | SD大鼠、Wistar大鼠、昆明小鼠、新西兰白兔、自发性高血压大鼠 | 神经功能评分;行为学测试(神经、肌肉运动功能、前庭运动功能);脑组织切片病理形态学观察 |
开颅电凝阻断法 | SD大鼠、BALB /c小鼠、新西兰白兔、巴马香猪、C57BL/6J小鼠 | 神经功能评分;行为学测试(神经、肌肉运动功能、前庭运动功能);脑组织切片病理形态学观察 |
光化学致血栓形成法 | 昆明小鼠、Wistar大鼠、食蟹猴 | 观察行为学变化;血脑屏障的完整性及梗塞面积观察;HE染色 |
血栓形成法 (自体血栓法) | 家犬、Beagle犬、Wistar大鼠、家兔 | 神经功能评分;脑组织切片病理形态学观察;测定脑组织含水量及梗死体积率 |
FeCl3致血栓形成法 | 新西兰白兔 | 行为改变;DSA图像表现;TTC染色测定脑梗死范围;脑组织切片病理形态学观察 |
栓子栓塞阻断法(硅胶柱/硅胶颗粒) | 家犬、新西兰白兔 | 行为学观察;大脑微血管造影;脑组织切片病理形态学观察查 |
栓子栓塞阻断法(月硅酸钠) | 新西兰白兔 | CT灌注成像;脑组织切片病理形态学观察 |
栓子栓塞阻断法(中药提取) | Wistar大鼠 | 神经功能障碍检查评分;脑组织切片病理形态学观察 |
内皮素-1灌注致血管收缩法 | SD大鼠 | 神经症状评分;24 h切出脑片,计算大脑半球体积及脑梗死体积;脑片作HE染色,计数存活神经元数 |
球囊导管法 | 猕猴 | 生命体征(体温、呼吸、心率);Task-oriented神经行为功能评分;磁共振扫描和血管成像,计算脑梗塞体积 |
2根血管闭塞法 | SD大鼠、长爪沙鼠 | 模型动物死亡率、行为学评分;脑组织细胞坏死率、凋亡率、炎症因子;脑组织切片病理形态学观察 |
3根血管闭塞法 | Wistar大鼠 | 模型动物意识形态、生命体征;脑组织切片病理形态学观察 |
4根血管闭塞法 | SD大鼠、日本大耳白兔、家猫、杂种犬、Wistar大鼠 | 模型动物生存情况、意识形态;脑组织切片病理形态学观察 |
心脏骤停法 | SD大鼠 | 脑组织切片病理形态学观察,行免疫组化观察脑内炎症指标 |
颈动脉分流法 | SD大鼠 | 脑电图检测;瞳孔颜色观察;平均动脉压;脑组织切片病理形态学观察 |
Table 1 Animal selection of ischemic stroke models
造模方法 | 模型动物 | 评价指标 |
---|---|---|
线栓法 | SD大鼠、Wistar大鼠、昆明小鼠、新西兰白兔、自发性高血压大鼠 | 神经功能评分;行为学测试(神经、肌肉运动功能、前庭运动功能);脑组织切片病理形态学观察 |
开颅电凝阻断法 | SD大鼠、BALB /c小鼠、新西兰白兔、巴马香猪、C57BL/6J小鼠 | 神经功能评分;行为学测试(神经、肌肉运动功能、前庭运动功能);脑组织切片病理形态学观察 |
光化学致血栓形成法 | 昆明小鼠、Wistar大鼠、食蟹猴 | 观察行为学变化;血脑屏障的完整性及梗塞面积观察;HE染色 |
血栓形成法 (自体血栓法) | 家犬、Beagle犬、Wistar大鼠、家兔 | 神经功能评分;脑组织切片病理形态学观察;测定脑组织含水量及梗死体积率 |
FeCl3致血栓形成法 | 新西兰白兔 | 行为改变;DSA图像表现;TTC染色测定脑梗死范围;脑组织切片病理形态学观察 |
栓子栓塞阻断法(硅胶柱/硅胶颗粒) | 家犬、新西兰白兔 | 行为学观察;大脑微血管造影;脑组织切片病理形态学观察查 |
栓子栓塞阻断法(月硅酸钠) | 新西兰白兔 | CT灌注成像;脑组织切片病理形态学观察 |
栓子栓塞阻断法(中药提取) | Wistar大鼠 | 神经功能障碍检查评分;脑组织切片病理形态学观察 |
内皮素-1灌注致血管收缩法 | SD大鼠 | 神经症状评分;24 h切出脑片,计算大脑半球体积及脑梗死体积;脑片作HE染色,计数存活神经元数 |
球囊导管法 | 猕猴 | 生命体征(体温、呼吸、心率);Task-oriented神经行为功能评分;磁共振扫描和血管成像,计算脑梗塞体积 |
2根血管闭塞法 | SD大鼠、长爪沙鼠 | 模型动物死亡率、行为学评分;脑组织细胞坏死率、凋亡率、炎症因子;脑组织切片病理形态学观察 |
3根血管闭塞法 | Wistar大鼠 | 模型动物意识形态、生命体征;脑组织切片病理形态学观察 |
4根血管闭塞法 | SD大鼠、日本大耳白兔、家猫、杂种犬、Wistar大鼠 | 模型动物生存情况、意识形态;脑组织切片病理形态学观察 |
心脏骤停法 | SD大鼠 | 脑组织切片病理形态学观察,行免疫组化观察脑内炎症指标 |
颈动脉分流法 | SD大鼠 | 脑电图检测;瞳孔颜色观察;平均动脉压;脑组织切片病理形态学观察 |
1 | PAUL S, CANDELARIO-JALIL E. Emerging neuroprotective strategies for the treatment of ischemic stroke: an overview of clinical and preclinical studies[J]. Exp Neurol, 2021, 335:113518. DOI: 10.1016/j.expneurol.2020.113518 . |
2 | 张昕, 秦冬冬, 尹勇. 啮齿类脑卒中动物模型的建立[J]. 中国康复, 2018, 33(2):152-155. DOI: 10.3870/zgkf.2018.02.019 . |
3 | 于洋, 朱雨岚. 缺血性脑卒中后血管生成研究的进展[J]. 心血管康复医学杂志, 2021, 30(1):99-102. DOI: 10.3969/j.issn.1008-0074.2021.01.26 . |
4 | 刘勇, 魏鑫甜, 陈伊. 局灶性脑缺血动物模型的制备探究[J]. 中国中医急症, 2019, 28(1):177-180, 185. DOI: 10.3969/j.issn.1004-745X.2019.01.056 . |
5 | 唐青青, 马勋泰. 缺血性卒中后癫痫动物模型的研究进展[J]. 癫痫杂志, 2020, 6(5):428-430. DOI: CNKI:SUN:DXZA.0.2020-05-010 . |
6 | 王晋晨, 熊晓星. 缺血性脑卒中动物模型研究进展[J]. 医学综述, 2020, 26(10):1881-1886, 1892. DOI: 10.3969/j.issn.1006-2084. 2020.10.002 . |
7 | KOIZMI J, YOSHID Y, NAKAZAWA T, et al.Experimental studies of ischemic brain edema: A new experimental model of cere-bral embolism in rats in which recirculation can be introduced in the ischemic area[J]. Stroke, 1986, 16(8):1-8. |
8 | LONGA E Z, WEINSTEIN P R, CARLSON S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1):84-91. DOI: 10.1161/01.str.20.1.84 . |
9 | SHI K, ZOU M, JIA D M, et al. tPA mobilizes immune cells that exacerbate hemorrhagic transformation in stroke[J]. Circ Res, 2021, 128(1):62-75. DOI: 10.1161/circresaha.120.317596 . |
10 | HERMANN D M, POPA-WAGNER A, KLEINSCHNITZ C, et al. Animal models of ischemic stroke and their impact on drug discovery[J]. Expert Opin Drug Discov, 2019, 14(3):315-326. DOI: 10.1080/17460441.2019.1573984 . |
11 | TAMURA A, GRAHAM D I, MCCULLOCH J, et al. Focal cerebral ischaemia in the rat: 1. description of technique and early neuropathological consequences following middle cerebral artery occlusion[J]. J Cereb Blood Flow Metab, 1981, 1(1):53-60. DOI: 10.1038/jcbfm.1981.6 . |
12 | KOLOSOWSKA N, GOTKIEWICZ M, DHUNGANA H, et al. Intracerebral overexpression of miR-669c is protective in mouse ischemic stroke model by targeting MyD88 and inducing alternative microglial/macrophage activation[J]. J Neuroinflammation, 2020, 17(1):194. DOI: 10.1186/s12974-020-01870-w . |
13 | CAI B, WANG N. Large animal stroke models vs. rodent stroke models, pros and cons, and combination?[J]. Acta Neurochir Suppl, 2016, 121:77-81. DOI: 10.1007/978-3-319-18497-5_13 . |
14 | WATSON B D, DIETRICH W D, BUSTO R, et al. Induction of reproducible brain infarction by photochemically initiated thrombosis[J]. Ann Neurol, 1985, 17(5):497-504. DOI:10.1002/ana.410170513 . |
15 | LEE J K, PARK M S, KIM Y S, et al. Photochemically induced cerebral ischemia in a mouse model[J]. Surg Neurol, 2007, 67(6):620-625; discussion 625. DOI: 10.1016/j.surneu.2006.08.077 . |
16 | HOFF E I, BLOKLAND A, RUTTEN K, et al. Dissociable effects in reaction time performance after unilateral cerebral infarction: a comparison between the left and right frontal cortices in rats[J]. Brain Res, 2006, 1069(1):182-189. DOI: 10.1016/j.brainres.2005.11.070 . |
17 | CHEN F, SUZUKI Y, NAGAI N, et al. Rodent stroke induced by photochemical occlusion of proximal middle cerebral artery: evolution monitored with MR imaging and histopathology[J]. Eur J Radiol, 2007, 63(1):68-75. DOI: 10.1016/j.ejrad.2007.01.005 . |
18 | 马浚宁, 高俊玮, 侯博儒, 等. 光化学栓塞法建立缺血性脑卒中动物模型[J]. 中国组织工程研究, 2015, 19(49):7951-7957. DOI: 10.3969/j.issn.2095-4344.2015.49.014 . |
19 | UZDENSKY A B. Photothrombotic stroke as a model of ischemic stroke[J]. Transl Stroke Res, 2018, 9(5):437-451. DOI: 10.1007/s12975-017-0593-8 . |
20 | LUO H Y, RAHMAN M, BOBROVSKAYA L, et al. The level of proBDNF in blood lymphocytes is correlated with that in the brain of rats with photothrombotic ischemic stroke[J]. Neurotox Res, 2019, 36(1):49-57. DOI: 10.1007/s12640-019-00022-0 . |
21 | SEQUEIRA E, PIERCE M L, AKASHEH D, et al. Epicortical brevetoxin treatment promotes neural repair and functional recovery after ischemic stroke[J]. Mar Drugs, 2020, 18(7):374. DOI: 10.3390/md18070374 . |
22 | BUSCH E, KRÜGER K, HOSSMANN K A. Improved model of thromboembolic stroke and rt-PA induced reperfusion in the rat[J]. Brain Res, 1997, 778(1):16-24. DOI: 10.1016/s0006-8993(97)01008-1 . |
23 | ARROYO A B, FERNÁNDEZ-PÉREZ M P, MONTE A DEL, et al. miR-146a is a pivotal regulator of neutrophil extracellular trap formation promoting thrombosis[J]. Haematologica, 2021, 106(6):1636-1646. DOI: 10.3324/haematol.2019.240226 . |
24 | OKADA Y, SHIMA T, YOKOYAMA N, et al. Comparison of middle cerebral artery trunk occlusion by silicone cylinder embolization and by trapping[J]. J Neurosurg, 1983, 58(4):492-499. DOI: 10.3171/jns.1983.58.4.0492 . |
25 | 张放, 姚振威, 冯晓源, 等. 急性兔脑栓塞模型的建立[J]. 中国实验动物学报, 2007, 15(6):458-460, 494. DOI: 10.3969/j.issn.1005-4847.2007.06.014 . |
26 | 尚华, 刘怀军, 雷建明, 等. 化学诱导兔脑缺血模型早期MSCT灌注成像实验性研究[J]. 河北医药, 2010, 32(17):2312-2314. DOI: 10.3969/j.issn.1002-7386.2010.17.002 . |
27 | 王俊涛, 田铧, 肖思建, 等. 中药白芨建立大鼠脑缺血模型可行性探讨[J]. 第四军医大学学报, 2007, 28(3):283-285. DOI: 10.3321/j.issn:1000-2790.2007.03.027 . |
28 | 程瑞新, 丁永红, 段承祥, 等. 中药白芨胶体建立急性脑梗塞模型[J]. 上海医学影像, 2001, 10(1):59-60. DOI: 10.3969/j.issn.1008-617X.2001.01.025 . |
29 | 芦金清, 张亚东. 白及胶的实验研究[J]. 中成药, 1996, 18(12): 2-3. |
30 | 郑传胜, 冯敢生, 张彦舫. 中药白芨胶作为血管栓塞剂的实验研究[J]. 中华放射学杂志, 1998, 32(3):43-46. DOI: 10.3760/j.issn:1005-1201.1998.03.014 . |
31 | 宋善俊, 王辨明, 沈迪, 等. 17种中草药体外血液凝固筛选实验研究[J]. 武汉医学院学报, 1977, 6(6):83-86, 89. |
32 | 葛勤, 刘同华, 黄林清. 中药白芨作为血管栓塞剂及药物载体的研究概况[J]. 中国药房, 2003, 14(5): 49-51. DOI: 10.3969/j.issn.1001-0408.2003.05.026 . |
33 | 张世红, 魏尔清, 朱朝阳, et al. 白三烯受体拮抗剂ONO-1078对内皮素-1诱导的大鼠局灶性脑缺血的保护作用[J]. 药学学报,2004(1). DOI:10.3321/j.issn:0513-4870.2004.01.001 . |
34 | GAO H M, LIU Y Q, LU S P, et al. A reversible middle cerebral artery occlusion model using intraluminal balloon technique in monkeys[J]. J Stroke Cerebrovasc Dis, 2006, 15(5):202-208. DOI: 10.1016/j.jstrokecerebrovasdis.2006.05.010 . |
35 | 郭云良, 高焕民, 李子祥, 等. 对微球囊栓塞大脑中动脉制作猕猴局灶性脑缺血再灌注模型的评价[J]. 解剖学报, 2008, 39(6):944-947. DOI: 10.3321/j.issn:0529-1356.2008.06.035 . |
36 | OHTANI R, TOMIMOTO H, KONDO T, et al. Upregulation of ceramide and its regulating mechanism in a rat model of chronic cerebral ischemia[J]. Brain Res, 2004, 1023(1):31-40. DOI: 10.1016/j.brainres.2004.07.024 . |
37 | 周好乐, 杜小燕, 路静, 等. 长爪沙鼠脑底动脉Willis环变异缺失遗传特性分析及脑缺血模型高发群体的初步培育[J]. 中国比较医学杂志, 2011, 21(8):40-43. DOI: 10.3969/j.issn.1671-7856. 2011.08.010 . |
38 | 田鹤邨, 陈前芬, 谢群. 三血管阻断与重开放造成的大鼠全脑缺血再灌流损伤的实验研究[J]. 蚌埠医学院学报, 1993, 18(2):113-117. DOI: CNKI:SUN:BANG.0.1993-02-019 . |
39 | PULSINELLI W A, BRIERLEY J B. A new model of bilateral hemispheric ischemia in the unanesthetized rat[J]. Stroke, 1979, 10(3):267-272. DOI: 10.1161/01.str.10.3.267 .[LinkOut] |
40 | 靖颖霞. 三种心脏骤停大鼠模型心肺复苏效果及脑损伤程度的研究[D]. 长沙: 中南大学, 2012: 45. |
41 | 花放, 丁晓慧, 刘文瑞, 等. 颈动脉负压分流制作大鼠全脑缺血/再灌注模型[J]. 中国实验动物学报, 2001, 9(1): 34-40. DOI: 10.3969/j.issn.1005-4847.2001.01.006 . |
42 | ALIENA-VALERO A, BAIXAULI-MARTÍN J, CASTELLÓ-RUIZ M, et al. Effect of uric acid in animal models of ischemic stroke: a systematic review and meta-analysis[J]. J Cereb Blood Flow Metab, 2021, 41(4):707-722. DOI: 10.1177/0271678x20967459 . |
43 | GRATE L L, GOLDEN J A, HOOPES P J, et al. Traumatic brain injury in piglets of different ages: techniques for lesion analysis using histology and magnetic resonance imaging[J]. J Neurosci Methods, 2003, 123(2):201-206. DOI: 10.1016/S0165-0270(02)00361-8 . |
44 | SAULEAU P, LAPOUBLE E, VAL-LAILLET D, et al. The pig model in brain imaging and neurosurgery[J]. Animal, 2009, 3(8):1138-1151. DOI: 10.1017/s1751731109004649 . |
45 | WHITE E, WOOLLEY M, BIENEMANN A, et al. A robust MRI-compatible system to facilitate highly accurate stereotactic administration of therapeutic agents to targets within the brain of a large animal model[J]. J Neurosci Methods, 2011, 195(1):78-87. DOI: 10.1016/j.jneumeth.2010.10.023 . |
46 | D'ARCEUIL H E, DE CRESPIGNY A J. Imaging stroke evolution after middle cerebral artery occlusion in non-human Primates[J]. Open Neuroimag J, 2011, 5:216-224. DOI: 10.2174/1874440001105010216 . |
47 | FLURI F, SCHUHMANN M K, KLEINSCHNITZ C. Animal models of ischemic stroke and their application in clinical research[J]. Drug Des Devel Ther, 2015, 9:3445-3454. DOI: 10.2147/DDDT.S56071 . |
48 | KAISER E E, WEST F D. Large animal ischemic stroke models: replicating human stroke pathophysiology[J]. Neural Regen Res, 2020, 15(8):1377-1387. DOI: 10.4103/1673-5374.274324 . |
49 | CANDELARIO-JALIL E, PAUL S. Impact of aging and comorbidities on ischemic stroke outcomes in preclinical animal models: a translational perspective[J]. Exp Neurol, 2021, 335:113494. DOI: 10.1016/j.expneurol.2020.113494 . |
50 | 王丹, 殷梅. 性激素与缺血性脑卒中关系的研究进展[J]. 医学综述, 2020, 26(23):4689-4693. DOI: 10.3969/j.issn.1006-2084. 2020.23.020 . |
51 | WANG J H, ZHANG P, TANG Z P. Animal models of transient ischemic attack: a review[J]. Acta Neurol Belg, 2020, 120(2):267-275. DOI: 10.1007/s13760-020-01295-5 . |
[1] | LIU Yayi, JIA Yunfeng, ZUO Yiming, ZHANG Junping, LÜ Shichao. Progress and Evaluation of Animal Model of Heart Qi-Yin Deficiency Syndrome [J]. Laboratory Animal and Comparative Medicine, 2025, 45(4): 411-421. |
[2] | ZHAO Xin, WANG Chenxi, SHI Wenqing, LOU Yuefen. Advances in the Application of Zebrafish in the Research of Inflammatory Bowel Disease Mechanisms and Drug Development [J]. Laboratory Animal and Comparative Medicine, 2025, 45(4): 422-431. |
[3] | PAN Yicong, JIANG Wenhong, HU Ming, QIN Xiao. Optimization of Surgical Procedure and Efficacy Evaluation of Aortic Calcification Model in Rats with Chronic Kidney Disease [J]. Laboratory Animal and Comparative Medicine, 2025, 45(3): 279-289. |
[4] | CHEN Yuhan, CHEN Jinling, LI Xin, OU Yanhua, WANG Si, CHEN Jingyi, WANG Xingyi, YUAN Jiali, DUAN Yuanyuan, YANG Zhongshan, NIU Haitao. Analysis of Animal Models of Myasthenia Gravis Based on Its Clinical Characteristics in Chinese and Western Medicine [J]. Laboratory Animal and Comparative Medicine, 2025, 45(2): 176-186. |
[5] | LIAN Hui, JIANG Yanling, LIU Jia, ZHANG Yuli, XIE Wei, XUE Xiaoou, LI Jian. Construction and Evaluation of a Rat Model of Abnormal Uterine Bleeding [J]. Laboratory Animal and Comparative Medicine, 2025, 45(2): 130-146. |
[6] | LUO Shixiong, ZHANG Sai, CHEN Hui. Research Progress in Establishment and Evaluation of Common Asthma Animal Models [J]. Laboratory Animal and Comparative Medicine, 2025, 45(2): 167-175. |
[7] | WANG Biying, LU Jiashuo, ZAN Guiying, CHEN Ruosong, CHAI Jingrui, LIU Jinggen, WANG Yujun. Establishment Methods and Application Progress of Rodent Models for Drug Addiction [J]. Laboratory Animal and Comparative Medicine, 2025, 45(2): 158-166. |
[8] | FEI Bin, GUO Wenke, GUO Jianping. Research Progress on Animal Models for Hernia Diseases and New Hernia Repair Materials [J]. Laboratory Animal and Comparative Medicine, 2025, 45(1): 55-66. |
[9] | YANG Jiahao, DING Chunlei, QIAN Fenghua, SUN Qi, JIANG Xusheng, CHEN Wen, SHEN Mengwen. Research Progress on Animal Models of Sepsis-Related Organ Injury [J]. Laboratory Animal and Comparative Medicine, 2024, 44(6): 636-644. |
[10] | SUN Xiaorong, SU Dan, GUI Wenjuan, CHEN Yue. Establishment and Evaluation of a Moderate-to-Severe Knee Osteoarthritis Model in Rats Induced by Surgery [J]. Laboratory Animal and Comparative Medicine, 2024, 44(6): 597-604. |
[11] | TIAN Fang, PAN Bin, SHI Jiayi, XU Yanyi, LI Weihua. Advances in Development of PM2.5-Exposed Animal Models and Their Application in Reproductive Toxicity Research [J]. Laboratory Animal and Comparative Medicine, 2024, 44(6): 626-635. |
[12] | ZHAO Xiaona, WANG Peng, YE Maoqing, QU Xinkai. Establishment of a New Hyperglycemic Obesity Cardiac Dysfunction Mouse Model with Triacsin C [J]. Laboratory Animal and Comparative Medicine, 2024, 44(6): 605-612. |
[13] | TU Yingxin, JI Yilan, WANG Fei, YANG Dongming, WANG Dongdong, SUN Zhixin, DAI Yuexin, WANG Yanji, Guanghan KAN, WU Bin, ZHAO Deming, YANG Lifeng. Evaluation of Simulated Weightlessness Model of Hindlimb Unloading Miniature Pigs and Their Tissue Damage [J]. Laboratory Animal and Comparative Medicine, 2024, 44(5): 475-486. |
[14] | HUANG Dongyan, WU Jianhui. Establishment Methods and Application Evaluation of Animal Models in Reproductive Toxicology Research [J]. Laboratory Animal and Comparative Medicine, 2024, 44(5): 550-559. |
[15] | ZHENG Qingyong, LI Tengfei, XU Jianguo, ZHOU Yongjia, MA Zhichao, WANG Na, LI Molan, YANG Wenjing, WU Peirun, WANG Haidong, TIAN Jinhui. Advances and Challenges in the Research of Integration Methods of Animal Experimental Evidence [J]. Laboratory Animal and Comparative Medicine, 2024, 44(5): 567-576. |
Viewed | ||||||
Full text |
|
|||||
Abstract |
|
|||||