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:: Volume 9, Issue 3 (Summer 2021) ::
Shefaye Khatam 2021, 9(3): 130-139 Back to browse issues page
A Review on the Experimental Animal Models of Cerebral Ischemia
Hamzeh Mirshekari Jahangiri , Ghazal Rahmani , Fariba Karimzadeh *
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran , Fariba_karimzade@yahoo.com
Abstract:   (2074 Views)
Introduction: Stroke is the third leading cause of death and the major cause of adult physical disability in the world. Despite advances in understanding the pathophysiological mechanisms of cerebral ischemia over the past few decades, the available therapies have not been effective for these patients. Nowadays, various animal models are used to study pathophysiology as well as risk factors, and to find therapeutic strategies for cerebral ischemia. These models divide into two forms: global cerebral ischemia and focal cerebral ischemia. Global ischemia models are divided into complete and incomplete models of ischemia, which are produced by occluding the cerebral blood flow completely or incompletely. Several focal cerebral ischemic stroke models have been developed in a variety of species that interrupt the blood flow to the brain in one or more areas of the brain. The vast majority of cerebral stroke cases are caused by transient or permanent occlusion of a cerebral blood vessel (ischemic stroke) eventually leading to brain infarction. The infarct size and the neurological outcome depend on a multitude of factors such as the duration and severity of ischemia, the existence of collateral systems, age, sex, and genetic background. Conclusion: Thus, ischemic stroke is a highly complex and heterogeneous disorder. It is obvious that experimental models of stroke cannot cover all the specific aspects of this disease. Therefore, the success of preclinical stroke research in developing new therapeutics for these patients might rely on the selection of the appropriate animal stroke model. This review deals with the most common stroke models and also discusses the advantages and limitations of each model.
Keywords: Ischemic Stroke, Brain Ischemia, Models, Animal
Full-Text [PDF 760 kb]   (759 Downloads)    
Type of Study: Review --- Open Access, CC-BY-NC | Subject: Basic research in Neuroscience
1. Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. The lancet. 2012; 380(9859): 2197-223. [DOI:10.1016/S0140-6736(12)61689-4]
2. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Executive summary: heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016; 133(4): 447-54. [DOI:10.1161/CIR.0000000000000366]
3. Lipton P. Ischemic cell death in brain neurons. Physiological reviews. 1999; 79(4): 1431-568. [DOI:10.1152/physrev.1999.79.4.1431]
4. Khoshnam SE, Winlow W, Farzaneh M, Farbood Y, Moghaddam HF. Pathogenic mechanisms following ischemic stroke. Neurological Sciences. 2017; 38(7): 1167-86. [DOI:10.1007/s10072-017-2938-1]
5. Zavvari F, Karimzadeh F. A Review on the Behavioral Tests for Learning and Memory Assessments in Rat. The Neuroscience Journal of Shefaye Khatam. 2017; 5(4): 110-24. [DOI:10.18869/acadpub.shefa.5.4.110]
6. Roth JM, editor Recombinant tissue plasminogen activator for the treatment of acute ischemic stroke. Baylor University Medical Center Proceedings; 2011: Taylor & Francis. [DOI:10.1080/08998280.2011.11928729]
7. Finsterer J. Central nervous system manifestations of mitochondrial disorders. Acta Neurologica Scandinavica. 2006; 114(4): 217-38. [DOI:10.1111/j.1600-0404.2006.00671.x]
8. Zavvari F, Karimzadeh F. A Methodological Review of Development and Assessment of Behavioral Models of Depression in Rats. The Neuroscience Journal of Shefaye Khatam. 2015; 3(4): 151-60. [DOI:10.18869/acadpub.shefa.3.4.151]
9. Khanizadeh A-M, Karimzadeh F. Experimental Models of Rheumatoid Arthritis: Acute and Chronic Pain. The Neuroscience Journal of Shefaye Khatam. 2017; 5(1): 98-109. [DOI:10.18869/acadpub.shefa.5.1.98]
10. Ginsberg MD, Busto R. Rodent models of cerebral ischemia. Stroke. 1989; 20(12): 1627-42. [DOI:10.1161/01.STR.20.12.1627]
11. Koizumi J. 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. Jpn J stroke. 1986; 8: 1-8.
12. Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. stroke. 1989; 20(1): 84-91. [DOI:10.1161/01.STR.20.1.84]
13. Meyer JS, Gotoh F, Tazaki Y. Circulation and metabolism following experimental cerebral embolism. Journal of Neuropathology & Experimental Neurology. 1962; 21(1): 4-24. [DOI:10.1097/00005072-196201000-00002]
14. Zhang Z, Zhang RL, Jiang Q, Raman SB, Cantwell L, Chopp M. A new rat model of thrombotic focal cerebral ischemia. Journal of Cerebral Blood Flow & Metabolism. 1997; 17(2): 123-35. [DOI:10.1097/00004647-199702000-00001]
15. Markgraf CG, Kraydieh S, Prado R, Watson BD, Dietrich WD, Ginsberg MD. Comparative histopathologic consequences of photothrombotic occlusion of the distal middle cerebral artery in Sprague-Dawley and Wistar rats. Stroke. 1993; 24(2): 286-92. [DOI:10.1161/01.STR.24.2.286]
16. Traystman RJ. Animal models of focal and global cerebral ischemia. ILAR journal. 2003; 44(2): 85-95. [DOI:10.1093/ilar.44.2.85]
17. Horn M, Schlote W. Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia. Acta neuropathologica. 1992; 85(1): 79-87. [DOI:10.1007/BF00304636]
18. Smith M-L, Auer R, Siesjö B. The density and distribution of ischemic brain injury in the rat following 2-10 min of forebrain ischemia. Acta neuropathologica. 1984; 64(4): 319-32. [DOI:10.1007/BF00690397]
19. Pulsinelli WA, Brierley JB, Plum F. Temporal profile of neuronal damage in a model of transient forebrain ischemia. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 1982; 11(5): 491-8. [DOI:10.1002/ana.410110509]
20. Choi K-E, Hall CL, Sun J-M, Wei L, Mohamad O, Dix TA, et al. A novel stroke therapy of pharmacologically induced hypothermia after focal cerebral ischemia in mice. The FASEB Journal. 2012; 26(7): 2799-810. [DOI:10.1096/fj.11-201822]
21. Pulsinelli WA, Levy DE, Duffy TE. Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 1982; 11(5): 499-509. [DOI:10.1002/ana.410110510]
22. Furlow Jr T. Cerebral ischemia produced by four-vessel occlusion in the rat: a quantitative evaluation of cerebral blood flow. Stroke. 1982; 13(6): 852-5. [DOI:10.1161/01.STR.13.6.852]
23. Sanderson TH, Wider JM. 2-vessel occlusion/hypotension: a rat model of global brain ischemia. JoVE (Journal of Visualized Experiments). 2013; (76): e50173. [DOI:10.3791/50173]
24. Atlasi MA, Naderian H, Noureddini M, Fakharian E, Azami A. Morphology of Rat Hippocampal CA1 neurons following modified two and four-vessels global ischemia models. Archives of trauma research. 2013; 2(3): 124. [DOI:10.5812/atr.10240]
25. Hawkins L. The experimental development of modern resuscitation. Resuscitation. 1972; 1(1): 9-24. [DOI:10.1016/0300-9572(72)90059-7]
26. Berkowitz ID, Gervais H, Schleien CL, Koehler RC, Dean JM, Traystman RJ. Epinephrine dosage effects on cerebral and myocardial blood flow in an infant swine model of cardiopulmonary resuscitation. Anesthesiology. 1991; 75(6): 1041-50. [DOI:10.1097/00000542-199112000-00017]
27. Michael J, Guerci A, Koehler RC, Shi A, Tsitlik J, Chandra N, et al. Mechanisms by which epinephrine augments cerebral and myocardial perfusion during cardiopulmonary resuscitation in dogs. Circulation. 1984; 69(4): 822-35. [DOI:10.1161/01.CIR.69.4.822]
28. Kofler J, Hattori K, Sawada M, DeVries AC, Martin LJ, Hurn PD, et al. Histopathological and behavioral characterization of a novel model of cardiac arrest and cardiopulmonary resuscitation in mice. Journal of neuroscience methods. 2004; 136(1): 33-44. [DOI:10.1016/j.jneumeth.2003.12.024]
29. Siemkowicz E, Hansen AJ. Clinical restitution following cerebral ischemia in hypo‐, normo‐and hyperglycemic rats. Acta neurologica scandinavica. 1978; 58(1): 1-8. [DOI:10.1111/j.1600-0404.1978.tb02855.x]
30. Kabat H, Dennis C, Baker A. Recovery of function following arrest of the brain circulation. American Journal of Physiology-Legacy Content. 1941; 132(3): 737-47. [DOI:10.1152/ajplegacy.1941.132.3.737]
31. Grenell RG. Central nervous system resistance; the effects of temporary arrest of cerebral circulation for periods of two to ten minutes. Obstetrical & Gynecological Survey. 1946; 1(5): 667. [DOI:10.1097/00006254-194610000-00048]
32. Jackson DL, Dole WP. Total cerebral ischemia: a new model system for the study of post-cardiac arrest brain damage. Stroke. 1979; 10(1): 38-43. [DOI:10.1161/01.STR.10.1.38]
33. Uzdensky AB. Photothrombotic stroke as a model of ischemic stroke. Translational stroke research. 2018; 9(5): 437-51. [DOI:10.1007/s12975-017-0593-8]
34. de Leciñana MA, Díez-Tejedor E, Carceller F, Roda JM. Cerebral ischemia: from animal studies to clinical practice. Should the methods be reviewed? Cerebrovascular Diseases. 2001; 11(Suppl. 1): 20-30. [DOI:10.1159/000049122]
35. Takizawa S, Hakim AM. Animal models of cerebral ischemia. 2. Rat models. Cerebrovascular Diseases. 1991; 1(Suppl. 1): 16-21. [DOI:10.1159/000108876]
36. Garcia JH. Experimental ischemic stroke: a review. Stroke. 1984; 15(1): 5-14. [DOI:10.1161/01.STR.15.1.5]
37. Hossmann K-A. Animal models of cerebral ischemia. 1. Review of literature. Cerebrovascular Diseases. 1991; 1(Suppl. 1): 2-15. [DOI:10.1159/000108875]
38. Tamura A, Graham D, McCulloch J, Teasdale G. Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. Journal of Cerebral Blood Flow & Metabolism. 1981; 1(1): 53-60. [DOI:10.1038/jcbfm.1981.6]
39. Popa-Wagner A, Schröder E, Schmoll H, Walker LC, Kessler C. Upregulation of MAP1B and MAP2 in the rat brain after middle cerebral artery occlusion: effect of age. Journal of Cerebral Blood Flow & Metabolism. 1999; 19(4): 425-34. [DOI:10.1097/00004647-199904000-00008]
40. Sugimori H, Yao H, Ooboshi H, Ibayashi S, Iida M. Krypton laser-induced photothrombotic distal middle cerebral artery occlusion without craniectomy in mice. Brain Research Protocols. 2004; 13(3): 189-96. [DOI:10.1016/j.brainresprot.2004.06.001]
41. Dirnagl U. Rodent models of stroke: Springer; 2010. [DOI:10.1007/978-1-60761-750-1]
42. Trueman RC, Harrison DJ, Dwyer DM, Dunnett SB, Hoehn M, Farr TD. A critical re-examination of the intraluminal filament MCAO model: impact of external carotid artery transection. Translational stroke research. 2011; 2(4): 651-61. [DOI:10.1007/s12975-011-0102-4]
43. McCabe C, Arroja MM, Reid E, Macrae IM. Animal models of ischaemic stroke and characterisation of the ischaemic penumbra. Neuropharmacology. 2018; 134: 169-77. [DOI:10.1016/j.neuropharm.2017.09.022]
44. Yanagisawa M, Kurihara H, Kimura S, Goto K, Masaki T. A novel peptide vasoconstrictor, endothelin, is produced by vascular endothelium and modulates smooth muscle Ca2+ channels. Journal of hypertension Supplement: official journal of the International Society of Hypertension. 1988; 6(4): S188-91. [DOI:10.1097/00004872-198812040-00056]
45. Fuxe K, Bjelke B, Andbjer B, Grahn H, Rimondini R, Agnati LF. Endothelin-1 induced lesions of the frontoparietal cortex of the rat. A possible model of focal cortical ischemia. Neuroreport. 1997; 8(11): 2623-9. [DOI:10.1097/00001756-199707280-00040]
46. Biernaskie J, Corbett D, Peeling J, Wells J, Lei H. A serial MR study of cerebral blood flow changes and lesion development following endothelin‐1‐induced ischemia in rats. Magnetic Resonance in Medicine: An Official Journal of the International Society for Magnetic Resonance in Medicine. 2001; 46(4): 827-30. [DOI:10.1002/mrm.1263]
47. Nakagomi S, Kiryu-Seo S, Kiyama H. Endothelin-converting enzymes and endothelin receptor B messenger RNAs are expressed in different neural cell species and these messenger RNAs are coordinately induced in neurons and astrocytes respectively following nerve injury. Neuroscience. 2000; 101(2): 441-9. [DOI:10.1016/S0306-4522(00)00345-6]
48. Moyanova S, Kortenska L, Kirov R, Iliev I. Quantitative electroencephalographic changes due to middle cerebral artery occlusion by endothelin 1 in conscious rats. Archives of physiology and biochemistry. 1998; 106(5): 384-91. [DOI:10.1076/apab.106.5.384.4362]
49. Kahvand Z, Edalatmanesh MA. The Effect of Trichostatin A on Working Memory and Serum Bcl-2 Level in Hypoxic-Ischemia Rat Model. The Neuroscience Journal of Shefaye Khatam. 2016; 4(4): 35-40. [DOI:10.18869/acadpub.shefa.4.4.35]
50. Alberts MJ, Atkinson R. Risk reduction strategies in ischaemic stroke : the role of antiplatelet therapy. Clinical drug investigation. 2004; 24(5): 245-54. [DOI:10.2165/00044011-200424050-00001]
51. Okamoto K, Aoki K. Development of a strain of spontaneously hypertensive rats. Japanese circulation journal. 1963; 27: 282-93. [DOI:10.1253/jcj.27.282]
52. Bailey EL, Smith C, Sudlow CL, Wardlaw JM. Is the spontaneously hypertensive stroke prone rat a pertinent model of sub cortical ischemic stroke? A systematic review. International journal of stroke : official journal of the International Stroke Society. 2011; 6(5): 434-44. [DOI:10.1111/j.1747-4949.2011.00659.x]
53. Johansson BB. Cerebral vascular bed in hypertension and consequences for the brain. Hypertension (Dallas, Tex : 1979). 1984; 6(6 Pt 2): Iii81-6. [DOI:10.1161/01.HYP.6.6_Pt_2.III81]
54. Hossmann K-A. Cerebral ischemia: models, methods and outcomes. Neuropharmacology. 2008; 55(3): 257-70. [DOI:10.1016/j.neuropharm.2007.12.004]
55. Rahimi M, Nameni F. Effects of Endurance Training and Adenosine on the Expression of the A2B Gene on the Ischemic-Reperfusion Model of the Male Rat Brain. The Neuroscience Journal of Shefaye Khatam. 2020; 9(1): 79-89.
56. Mayzel‐Oreg O, Omae T, Kazemi M, Li F, Fisher M, Cohen Y, et al. Microsphere‐induced embolic stroke: An MRI study. Magnetic Resonance in Medicine: An Official Journal of the International Society for Magnetic Resonance in Medicine. 2004; 51(6): 1232-8. [DOI:10.1002/mrm.20100]
57. Niessen F, Hilger T, Hoehn M, Hossmann K-A. Differences in clot preparation determine outcome of recombinant tissue plasminogen activator treatment in experimental thromboembolic stroke. Stroke. 2003; 34(8): 2019-24. [DOI:10.1161/01.STR.0000080941.73934.30]
58. Wang CX, Todd KG, Yang Y, Gordon T, Shuaib A. Patency of cerebral microvessels after focal embolic stroke in the rat. Journal of Cerebral Blood Flow & Metabolism. 2001; 21(4): 413-21. [DOI:10.1097/00004647-200104000-00010]
59. Ishikawa M, Sekizuka E, Oshio C, Sato S, Yamaguchi N, Terao S, et al. Platelet adhesion and arteriolar dilation in the photothrombosis: observation with the rat closed cranial and spinal windows. Journal of the neurological sciences. 2002; 194(1): 59-69. [DOI:10.1016/S0022-510X(01)00673-6]
60. Watson BD, Dietrich WD, Busto R, Wachtel MS, Ginsberg MD. Induction of reproducible brain infarction by photochemically initiated thrombosis. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 1985; 17(5): 497-504. [DOI:10.1002/ana.410170513]
61. Uzdensky A. Photothrombotic stroke as a model of ischemic stroke. Transl Stroke Res 9: 437-451. 2018. [DOI:10.1007/s12975-017-0593-8]

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Mirshekari Jahangiri H, Rahmani G, Karimzadeh F. A Review on the Experimental Animal Models of Cerebral Ischemia. Shefaye Khatam 2021; 9 (3) :130-139
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مجله علوم اعصاب شفای خاتم The Neuroscience Journal of Shefaye Khatam
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