Animal Models of Ischemic Stroke

  • Harpreet Kaur
  • Deepaneeta Sarmah
  • Kiran Kalia
  • Anupom Borah
  • Kunjan R. Dave
  • Dileep R. Yavagal
  • Pallab Bhattacharya


Stroke is the second leading cause of death worldwide. Up to 80% of strokes are ischemic and take place due to occlusion of major cerebral arteries or its branches. The pathophysiology of stroke is multifaceted, involving excitotoxicity and activation of inflammatory pathways leading to disturbances in ion channels, oxidative damage, and apoptosis. Thrombolytics are the only FDA-approved drug for ischemic stroke. In order to study the pathophysiology, development of a reliable and reproducible model of ischemic stroke is of great importance. The ideal animal model is the one which can mimic the features of the pathology. This chapter summarizes the models of ischemic stroke with its advantages and limitations.


Middle cerebral artery occlusion Craniectomy Photothrombosis Endothelin-1 Embolic stroke model 


  1. 1.
    Fluri F, Schuhmann MK, Kleinschnitz C (2015) Animal models of ischemic stroke and their application in clinical research. Drug Des Dev Ther 9:3445Google Scholar
  2. 2.
    Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79(4):1431–1568CrossRefGoogle Scholar
  3. 3.
    Fisher M (2004) The ischemic penumbra: identification, evolution and treatment concepts. Cerebrovasc Dis 17(Suppl 1):1–6CrossRefGoogle Scholar
  4. 4.
    Adams HP Jr et al (2007) Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Circulation 115(20):e478–e534CrossRefGoogle Scholar
  5. 5.
    Fonarow GC et al (2011) Timeliness of tissue-type plasminogen activator therapy in acute ischemic stroke: patient characteristics, hospital factors, and outcomes associated with door-to-needle times within 60 minutes. Circulation 123(7):750–758CrossRefGoogle Scholar
  6. 6.
    Durukan A, Tatlisumak T (2008) Animal models of ischemic stroke. Handb Clin Neurol 92:43–66CrossRefGoogle Scholar
  7. 7.
    McAuley M (1995) Rodent models of focal ischemia. Cerebrovasc Brain Metab Rev 7(2):153–180PubMedGoogle Scholar
  8. 8.
    Sevick R et al (1990) Diffusion-weighted MR imaging and T2-weighted MR imaging in acute cerebral ischaemia: comparison and correlation with histopathology. In: Brain edema VIII. Springer, New York, pp 210–212CrossRefGoogle Scholar
  9. 9.
    Fisher M et al (2009) Update of the stroke therapy academic industry roundtable preclinical recommendations. Stroke 40(6):2244–2250CrossRefGoogle Scholar
  10. 10.
    Wang L, Qin C, Yang G-Y (2017) Animal models for ischemic stroke. In: Translational research in stroke. Springer, New York, pp 357–379CrossRefGoogle Scholar
  11. 11.
    Bogousslavsky J, Van Melle G, Regli F (1988) The Lausanne Stroke Registry: analysis of 1,000 consecutive patients with first stroke. Stroke 19(9):1083–1092CrossRefGoogle Scholar
  12. 12.
    Howells DW et al (2010) Different strokes for different folks: the rich diversity of animal models of focal cerebral ischemia. J Cereb Blood Flow Metab 30(8):1412–1431CrossRefGoogle Scholar
  13. 13.
    Longa EZ et al (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20(1):84–91CrossRefGoogle Scholar
  14. 14.
    Liu S et al (2009) Rodent stroke model guidelines for preclinical stroke trials. J Exp Stroke Transl Med 2(2):2CrossRefGoogle Scholar
  15. 15.
    Trueman RC et al (2011) A critical re-examination of the intraluminal filament MCAO model: impact of external carotid artery transection. Transl Stroke Res 2(4):651–661CrossRefGoogle Scholar
  16. 16.
    Tsuchiya D et al (2003) Effect of suture size and carotid clip application upon blood flow and infarct volume after permanent and temporary middle cerebral artery occlusion in mice. Brain Res 970(1–2):131–139CrossRefGoogle Scholar
  17. 17.
    McCabe C et al (2018) Animal models of ischaemic stroke and characterisation of the ischaemic penumbra. Neuropharmacology 134:169–177CrossRefGoogle Scholar
  18. 18.
    Guan Y et al (2012) Effect of suture properties on stability of middle cerebral artery occlusion evaluated by synchrotron radiation angiography. Stroke 43(3):888–891CrossRefGoogle Scholar
  19. 19.
    Yuan F et al (2012) Optimizing suture middle cerebral artery occlusion model in C57BL/6 mice circumvents posterior communicating artery dysplasia. J Neurotrauma 29(7):1499–1505CrossRefGoogle Scholar
  20. 20.
    Sommer CJ (2017) Ischemic stroke: experimental models and reality. Acta Neuropathol 133(2):245–261CrossRefGoogle Scholar
  21. 21.
    Shigeno T et al (1985) Recirculation model following MCA occlusion in rats: cerebral blood flow, cerebrovascular permeability, and brain edema. J Neurosurg 63(2):272–277CrossRefGoogle Scholar
  22. 22.
    Buchan AM, Xue D, Slivka A (1992) A new model of temporary focal neocortical ischemia in the rat. Stroke 23(2):273–279CrossRefGoogle Scholar
  23. 23.
    Sugimori H et al (2004) Krypton laser-induced photothrombotic distal middle cerebral artery occlusion without craniectomy in mice. Brain Res Protocol 13(3):189–196CrossRefGoogle Scholar
  24. 24.
    Tamura A et al (1981) Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab 1(1):53–60CrossRefGoogle Scholar
  25. 25.
    Yanamoto H et al (2003) Evaluation of MCAO stroke models in normotensive rats: standardized neocortical infarction by the 3VO technique. Exp Neurol 182(2):261–274CrossRefGoogle Scholar
  26. 26.
    Göb E et al (2015) Blocking of plasma kallikrein ameliorates stroke by reducing thromboinflammation. Ann Neurol 77(5):784–803CrossRefGoogle Scholar
  27. 27.
    Watson BD et al (1985) Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol 17(5):497–504CrossRefGoogle Scholar
  28. 28.
    Kleinschnitz C et al (2008) Blocking of platelets or intrinsic coagulation pathway–driven thrombosis does not prevent cerebral infarctions induced by photothrombosis. Stroke 39(4):1262–1268CrossRefGoogle Scholar
  29. 29.
    Dietrich WD et al (1986) Photochemically induced cortical infarction in the rat. 1. Time course of hemodynamic consequences. J Cereb Blood Flow Metab 6(2):184–194CrossRefGoogle Scholar
  30. 30.
    Qian C et al (2016) Precise characterization of the penumbra revealed by MRI: a modified photothrombotic stroke model study. PLoS One 11(4):e0153756CrossRefGoogle Scholar
  31. 31.
    Lee VM et al (1996) Evolution of photochemically induced focal cerebral ischemia in the rat. Magnetic resonance imaging and histology. Stroke 27(11):2110–2118; discussion 2118-9CrossRefGoogle Scholar
  32. 32.
    Provenzale JM et al (2003) Assessment of the patient with hyperacute stroke: imaging and therapy. Radiology 229(2):347–359CrossRefGoogle Scholar
  33. 33.
    Macrae IM et al (1993) Endothelin-1-induced reductions in cerebral blood flow: dose dependency, time course, and neuropathological consequences. J Cereb Blood Flow Metab 13(2):276–284CrossRefGoogle Scholar
  34. 34.
    Lecrux C et al (2008) Effects of magnesium treatment in a model of internal capsule lesion in spontaneously hypertensive rats. Stroke 39(2):448–454CrossRefGoogle Scholar
  35. 35.
    Zhang L et al (2015) Focal embolic cerebral ischemia in the rat. Nat Protoc 10(4):539CrossRefGoogle Scholar
  36. 36.
    Hossmann K-A (2008) Cerebral ischemia: models, methods and outcomes. Neuropharmacology 55(3):257–270CrossRefGoogle Scholar
  37. 37.
    Mayzel-Oreg O et al (2004) Microsphere-induced embolic stroke: an MRI study. Magn Reson Med 51(6):1232–1238CrossRefGoogle Scholar
  38. 38.
    Gerriets T et al (2003) The macrosphere model: evaluation of a new stroke model for permanent middle cerebral artery occlusion in rats. J Neurosci Methods 122(2):201–211CrossRefGoogle Scholar
  39. 39.
    Macrae I (2011) Preclinical stroke research–advantages and disadvantages of the most common rodent models of focal ischaemia. Br J Pharmacol 164(4):1062–1078CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Harpreet Kaur
    • 1
  • Deepaneeta Sarmah
    • 1
  • Kiran Kalia
    • 1
  • Anupom Borah
    • 2
  • Kunjan R. Dave
    • 3
  • Dileep R. Yavagal
    • 4
  • Pallab Bhattacharya
    • 1
  1. 1.Department of Pharmacology and ToxicologyNational Institute of Pharmaceutical Education and Research-Ahmedabad (NIPER-A)GandhinagarIndia
  2. 2.Department of Life Science and BioinformaticsAssam UniversitySilcharIndia
  3. 3.Department of NeurologyUniversity of Miami Miller School of MedicineMiamiUSA
  4. 4.Department of Neurology and NeurosurgeryUniversity of Miami Miller School of MedicineMiamiUSA

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