Brief analysis of the frequency of use and spectrum of animal models in stroke research

Authors: J. Hložková 1,2;  V. Juračková 2;  P. Suchý Jr. 2;  P. Scheer 1,2;  R. Mikulík 1
Published in the journal: Cesk Slov Neurol N 2019; 115(3): 274-278
Category: Přehledný referát
doi: 10.14735/amcsnn2019274


Aim: The development of new drugs and curative treatments without animal models is currently not possible. Due to the unique complexity of stroke, the number of models studying this is unusually extensive. The aim of the overview is to describe and simply analyse used experimental models and commonly used animal species in research in vascular events.

Methods: The publications were searched in November 2017 in databases: PubMed, Science Direct, Wiley Online Library and Springer Link by using key word combinations. There was the registered type of model, species of animal, its gender and age of the animal for each stroke model, and there was the registered frequency of occurrence in monitored publication databases. Relevant publications and duplications were not excluded.

Results: There were 3,093 relevant links from 26,198 articles, which correspond to the specification of the methodology. The results were processed in an overviewed table.

Conclusion: The article maps the frequency of use of animal models and used animal species in the field of stroke.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.


animal stroke model – rat – mouse – rabbit – sheep – pig – gerbil – cat – dog – non-human primates


1. Donner L, Hrbková J. The tissue plasminogen activator and plasma fibrinolysis in diet induced lipemia in rats. Folia Haematol Int Mag Klin Morphol Blutforsch 1974; 101(4): 647–653.

2. Fletcher AP, Alkjaersig N, Lewis M et al. A pilot study of urokinase therapy in cerebral infarction. Stroke 1976; 7(2): 135–142.

3. Zivin JA, Fisher M, DeGirolami U et al. Tissue plasminogen activator reduces neurological damage after cerebral embolism. Science 1985; 230(4731): 1289–1292.

4. Archer DP, Walker AM, McCann SK et al. Anesthetic neuroprotection in experimental stroke in rodents: a systematic review and meta-analysis. Anesthesiology 2017; 126(4): 653–665. doi: 10.1097/ALN.0000000000001534.

5. Stroke Therapy Academic Industry Roundtable (STAIR). Recommendations for standards regarding preclinical neuroprotective and restorative drug development. Stroke 1999; 30(12): 2752–2758.

6. Sommer CJ. Ischemic stroke: experimental models and reality. Acta Neuropathol 2017; 133(2): 245–261. doi: 10.1007/s00401-017-1667-0.

7. Součková L, Kostkova H, Demlova R. Jak se vyvíjí nový lék. Prakt Lékáren 2015; 11(4): 144–147.

8. Marshall JW, Cummings RM, Bowes LJ et al. Functional and histological evidence for the protective effect of NXY-059 in a primate model of stroke when given 4 hours after occlusion. Stroke 2003; 34(9): 2228–2233. doi: 10.1161/01.STR.0000087790.79851.A8.

9. Shuaib A, Lees KR, Lyden P et al. SAINT II Trial Investigators NXY-059 for the treatment of acute ischemic stroke. N Engl J Med 2007; 357(6): 562–571. doi: 10.1056/NEJMoa070240.

10. PubMed. [online]. Available from URL:

11. ScienceDirect. [online]. Available form URL:

12. Wiley Online Library. [online]. Available from URL:

13. Springer Link. [online]. Available form URL:

14. Kim SK, Cho KO, Kim SY. The plasticity of posterior communicating artery influences on the outcome of white matter injury induced by chronic cerebral hypoperfusion in rats. Neurol Res 2009; 31(3): 245–250. doi: 10.1179/174313209X382278.

15. Herrmann M, Stern M, Vollenweider F et al. Effect of inherent epileptic seizures on brain injury after transient cerebral ischemia in Mongolian gerbils. Exp Brain Res 2004; 154(2): 176–182. doi: 10.1007/s00221-003-1655-6.

16. Paschen W, Djuricic BM, Bosma HJ et al. Biochemical changes during graded brain ischemia in gerbils. Part 2. Regional evaluation of cerebral blood flow and brain metabolites. J Neurol Sci 1983; 58(1): 37–44.

17. Atchaneeyasakul K, Guada L, Ramdas K et al. Large animal canine endovascular ischemic stroke models: a review. Brain Res Bull 2016; 127: 134–140. doi: 10.1016/j.brainresbull.2016.07.006.

18. Gray-Edwards HL, Salibi N, Josephson EM et al. High resolution MRI anatomy of the cat brain at 3 Tesla. J Neurosci Methods 2014; 227: 10–17. doi: 10.1016/j.jneumeth.2014.01.035.

19. Cai B, Wang N. Large animal stroke models vs. rodent stroke models, pros and cons, and combination? Acta Neurochir Suppl 2016; 121: 77–81. doi: 10.1007/978-3-319-18497-5_13.

20. Popesko (eds). Anatómia hospodárských zvierat. Bratislava, SK: Príroda 1992.

21. Arikan F, Martínez-Valverde T, Sánchez-Guerrero Á et al. Malignant infarction of the middle cerebral artery in a porcine model. A pilot study. PLoS One 2017; 12(2): e0172637. doi: 10.1371/journal.pone.0172637.

22. Cook DJ, Tymianski M. Nonhuman primate models of stroke for translational neuroprotection research. Neurotherapeutics 2012; 9(2): 371–379. doi: 10.1007/s13311-012-0115-z.

23. Watson BD, Dietrich WD, Busto R et al. Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol 1985; 17(5): 497–504. doi: 10.1002/ana.410170513.

24. Fieschi C, Battistini N, Volante F et al. Animal model of TIA: an experimental study with intracarotid ADP infusion in rabbits. Stroke 1975; 6(6): 617–621.

25. Furlow TW Jr, Bass NH. Cerebral hemodynamics in the rat assessed by a non-diffusible indicator-dilution technique. Brain Res 1976; 110(2): 366–370.

26. Mayzel-Oreg O, Omae T, Kazemi M et al. Microsphere-induced embolic stroke: an MRI study. Magn Reson Med 2004; 51(6): 1232–1238. doi: 10.1002/mrm.20100.

27. Winding O. Cerebral microembolization following carotid injection of dextran microspheres in rabbits. Neuroradiology 1981; 21(3): 123–126.

28. Nagano H, Suzuki T, Hayashi M et al. Cerebral microcirculatory changes after cerebral embolization induced by glass bead injection in rabbits. Angiology 1992; 43(8): 678–684. doi: 10.1177/000331979204300808.

29. Demura N, Mizukawa K, Ogawa N et al. A cerebral ischemia model produced by injection of microspheres via the external carotid artery in freely moving rats. Neurosci Res 1993; 17(1): 23–30.

30. Koizumi J, Yoshida Y, Nakazawa T et al. Experimental studies of ischemic brain edema. 1. A new experimental model of cerebral embolism in rats in which recirculation can be introduced in the ischemic area. Jap J Stroke 1986; 8(1), 1–8.

31. Mies G, Ishimaru S, Xie Y et al. Ischemic thresholds of cerebral protein synthesis and energy state following middle cerebral artery occlusion in rat. J Cereb Blood Flow Metab 1991; 11(5): 753–761. doi: 10.1038/jcbfm.1991.132.

32. Zhao Q, Memezawa H, Smith ML et al. Hyperthermia complicates middle cerebral artery occlusion induced by an intraluminal filament. Brain Res 1994; 649(1–2): 253–259.

33. Wang-Fischer Y(eds). Manual of stroke models in rats. London GB: CRC Press 2009.

34. Kilic E, Hermann DM, Hossmann KA. A reproducible model of thromboembolic stroke in mice. Neuroreport 1998; 9(13): 2967–2970.

35. Hossmann KA. Cerebral ischemia: models, methods and outcomes. Neuropharmacology 2008; 55(3): 257–270. doi: 10.1016/j.neuropharm.2007.12.004.

36. Morancho A, García-Bonilla L, Barceló V et al. A new method for focal transient cerebral ischaemia by distal compression of the middle cerebral artery. Neuropathol Appl Neurobiol 2012; 38(6): 617–627. doi: 10.1111/j.1365-2990.2012.01252.x.

37. Huang J, Mocco J, Choudhri TF et al. A modified transorbital baboon model of reperfused stroke. Stroke 2000; 31(12): 3054–3063.

38. Yamori Y, Horie R, Handa H et al. Pathogenetic similarity of strokes in stroke-prone spontaneously hypertensive rats and humans. Stroke 1976; 7(1): 46–53.

39. Coyle P, Jokelainen PT. Differential outcome to middle cerebral artery occlusion in spontaneously hypertensive stroke-prone rats (SHRSP) and Wistar Kyoto (WKY) rats. Stroke 1983; 14(4): 605–611.

40. Zeng J, Zhang Y, Mo J et al. Two-kidney, two clip renovascular hypertensive rats can be used as stroke-prone rats. Stroke 1998; 29(8): 1708–1713.

41. MacLellan CL, Silasi G, Auriat AM et al. Rodent models of intracerebral hemorrhage. Stroke 2010; 41(10 Suppl): S95–S98. doi: 10.1161/STROKEAHA.110.594457.

42. Becker KJ. Strain-related differences in the immune response: relevance to human stroke. Transl Stroke Res 2016; 7(4): 303–312. doi: 10.1007/s12975-016-0455-9.

43. Fox G, Gallacher D, Shevde S et al. Anatomic variation of the middle cerebral artery in the Sprague-Dawley rat. Stroke 1993; 24(12): 2087–2092.

44. Krafft PR, Bailey EL, Lekic T et al. Etiology of stroke and choice of models. Int J Stroke 2012; 7(5): 398–406. doi: 10.1111/j.1747-4949.2012.00838.x.

45. Robinson RG. Differential behavioral and biochemical effects of right and left hemispheric cerebral infarction in the rat. Science 1979; 205(4407): 707–710.

46. Lapchak PA. Translational stroke research using a rabbit embolic stroke model: a correlative analysis hypothesis for novel therapy development. Transl Stroke Res 2010; 1(2): 96–107. doi: 10.1007/s12975-010-0018-4.

Dětská neurologie Neurochirurgie Neurologie
Článek Editorial

Článek vyšel v časopise

Česká a slovenská neurologie a neurochirurgie

Číslo 3

2019 Číslo 3

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