Rabbit models of ischemic stroke in biomedical research

Abstract


The development of experimental models of ischemic stroke allowing for effective translation of results from animal studies to humans is an important task of modern neuropharmacology. Due to the fact that new drugs with neuroprotective properties that have shown activity in rodents most often turn out to be not effective enough in humans, the use of larger laboratory animals may become a viable solution. Among the latter, rabbits are the most accessible species for laboratories. Since they have gyrencephalic brains and a significant amount of white matter, they can be considered to be highly similar to humans. In the present review, we discussed the main methods of ischemic stroke modelling in rabbits. The breed, age and sex of the animals, anesthesia methods as well as criteria for functional state assessment after cerebral ischemia are the issues that should be addressed before the start of the study.


Yuriy I. Sysoev

Saint-Petersburg Chemical-Pharmaceutical University, St. Petersburg

Author for correspondence.
Email: susoyev92@mail.ru
ORCID iD: 0000-0003-4199-5318
SPIN-code: 3359-7902

Russian Federation, 197376, St. Petersburg, Professora Popova st., 14

senior lecturer at the Department of Pharmacology and Clini-cal Pharmacology

Veronika A. Prikhodko

Saint-Petersburg Chemical-Pharmaceutical University, St. Petersburg

Email: veronika.prihodko@pharminnotech.com
ORCID iD: 0000-0002-4690-1811
SPIN-code: 4774-9096

Russian Federation, 197376, St. Petersburg, Professora Popova st., 14

graduate student at the Department of Pharmacology and Clinical Pharmacology

Dmitry Y. Ivkin

Saint-Petersburg Chemical-Pharmaceutical University, St. Petersburg

Email: dmitry.ivkin@pharminnotech.com
ORCID iD: 0000-0001-9273-6864
SPIN-code: 9981-9772

Russian Federation, 197376, St. Petersburg, Professora Popova st., 14

PhD of Biological Sciences , Аssociate Professor at the Depart-ment of Pharmacology and Clinical Pharmacology

Sergey Okovity

Saint-Petersburg Chemical-Pharmaceutical University, St. Petersburg

Email: sergey.okovity@pharminnotech.com
ORCID iD: 0000-0003-4294-5531
SPIN-code: 7922-6882

Russian Federation, 197376, St. Petersburg, Professora Popova st., 14

PhD in Medicine, Professor, head of the Department of Pharma-cology and Clinical Pharmacology

  1. Donkor E. Stroke in the 21st century: A snapshot of the burden, epidemiology, and quality of life. Stroke Res Treat. 2018;2018:1-10. doi: 10.1155/2018/3238165
  2. Murray C, Vos T, Lozano R 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):2197-2223. doi: 10.1016/s0140-6736(12)61689-4
  3. Торяник И. И., Колесник В. В. Унифицированный подход к созданию модели ишемического инсульта головного мозга в эксперименте на крысах линии Вистар //Актуальні проблеми сучасної медицини: Вісник української медичної стоматологічної академії. – 2010. – Т. 10. – №. 4 (32). [Torianik II, Kolesnik VV. Unified approach in creation of cerebral ischemic stroke model in Wistar rats. Aktual'nі problemi suchasnoї meditsini: Vіsnik ukraїns'koї medichnoї stomatologіchnoї akademії. 2010;10(4):155-159]
  4. Maeda K, Hata R, Hossmann K. Regional metabolic disturbances and cerebrovascular anatomy after permanent middle cerebral artery occlusion in C57Black/6 and SV129 mice. Neurobiol Dis. 1999;6(2):101-108. doi: 10.1006/nbdi.1998.0235
  5. Ito U, Hakamata Y, Yamaguchi T, Ohno K. Cerebral ischemia model using mongolian gerbils — comparison between unilateral and bilateral carotid occlusion models. Brain Edema XV. 2013:17-21. doi: 10.1007/978-3-7091-1434-6_3
  6. Kleinschnitz C, Fluri F, Schuhmann M. Animal models of ischemic stroke and their application in clinical research. Drug Des Devel Ther. 2015:3445. doi: 10.2147/dddt.s56071
  7. Hoyte L, Kaur J, Buchan A. Lost in translation: taking neuroprotection from animal models to clinical trials. Exp Neurol. 2004;188(2):200-204. doi: 10.1016/j.expneurol.2004.05.008
  8. Jeon J, Jung H, Jang H et al. Canine model of ischemic stroke with permanent middle cerebral artery occlusion: clinical features, magnetic resonance imaging, histopathology, and immunohistochemistry. J Vet Sci. 2015;16(1):75. doi: 10.4142/jvs.2015.16.1.75
  9. García JH, Kalimo H, Kamijyo Y, Trump BF. Cellular events during partial cerebral ischemia. I. Electron microscopy of feline cerebral cortex after middle-cerebral-artery occlusion. Virchows Arch B Cell Pathol. 1977;25(3):191-206
  10. Zhang L, Cheng H, Shi J, Chen J. Focal epidural cooling reduces the infarction volume of permanent middle cerebral artery occlusion in swine. Surg Neurol. 2007;67(2):117-121. doi: 10.1016/j.surneu.2006.05.064
  11. Boltze J, Förschler A, Nitzsche B et al. Permanent middle cerebral artery occlusion in sheep: a novel large animal model of focal cerebral ischemia. Journal of Cerebral Blood Flow & Metabolism. 2008;28(12):1951-1964. doi: 10.1038/jcbfm.2008.89
  12. Ji X, Zhao B, Shang G et al. A more consistent intraluminal rhesus monkey model of ischemic stroke. Neural Regen Res. 2014;9(23):2087. doi: 10.4103/1673-5374.147936
  13. Sorby-Adams A, Vink R, Turner R. Large animal models of stroke and traumatic brain injury as translational tools. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2018;315(2):R165-R190. doi: 10.1152/ajpregu.00163.2017
  14. Liu F, McCullough L. Middle cerebral artery occlusion model in rodents: methods and potential pitfalls. Journal of Biomedicine and Biotechnology. 2011;2011:1-9. doi: 10.1155/2011/464701
  15. Chen F, Long Z, Yin J, Zuo Z, Li H. Isoflurane post-treatment improves outcome after an embolic stroke in rabbits. PLoS ONE. 2015;10(12):e0143931. doi: 10.1371/journal.pone.0143931
  16. Culp W, Brown A, Lowery J, Arthur M, Roberson P, Skinner R. Dodecafluoropentane emulsion extends window for tPA therapy in a rabbit stroke model. Mol Neurobiol. 2015;52(2):979-984. doi: 10.1007/s12035-015-9243-x
  17. Hao C, Ding W, Xu X et al. Effect of recombinant human prourokinase on thrombolysis in a rabbit model of thromboembolic stroke. Biomed Rep. 2017. doi: 10.3892/br.2017.1013
  18. Lapchak P, Boitano P, Bombien R et al. CNB-001, a pleiotropic drug is efficacious in embolized agyrencephalic New Zealand white rabbits and ischemic gyrencephalic cynomolgus monkeys. Exp Neurol. 2019;313:98-108. doi: 10.1016/j.expneurol.2018.11.010
  19. Arthur M, Brown A, Carlson K, Lowery J, Skinner R, Culp W. Dodecafluoropentane improves neurological function following anterior ischemic stroke. Mol Neurobiol. 2016;54(6):4764-4770. doi: 10.1007/s12035-016-0019-8
  20. English J, Hetts S, El-Ali A et al. A novel model of large vessel ischemic stroke in rabbits: microcatheter occlusion of the posterior cerebral artery. J Neurointerv Surg. 2014;7(5):363-366. doi: 10.1136/neurintsurg-2013-011063
  21. Yang J, Liu H, Liu R. A modified rabbit model of stroke: evaluation using clinical MRI scanner. Neurol Res. 2009;31(10):1092-1096. doi: 10.1179/174313209x405100
  22. Yang L, Liu W, Chen R et al. In Vivo Bioimpedance spectroscopy characterization of healthy, hemorrhagic and ischemic rabbit brain within 10 Hz–1 MHz. Sensors. 2017;17(4):791. doi: 10.3390/s17040791
  23. Yamamoto K, Yoshimine T, Yanagihara T. Cerebral ischemia in rabbit: a new experimental model with immunohistochemical investigation. Journal of Cerebral Blood Flow & Metabolism. 1985;5(4):529-536. doi: 10.1038/jcbfm.1985.80
  24. Wakayama A, Graf R, Rosner G, Heiss WD. Deafferentation versus cortical ischemia in a rabbit model of middle cerebral artery occlusion. Stroke. 1989;20(8):1071-1078. doi: 10.1161/01.str.20.8.1071
  25. Zivin JA, Fisher M, DeGirolami U, Hemenway CC, Stashak JA. Tissue plasminogen activator reduces neurological damage after cerebral embolism. Science. 1985;230(4731):1289-1292. doi: 10.1126/science.3934754
  26. Lapchak PA, Daley JT, Boitano PD. A blinded, randomized study of l-arginine in small clot embolized rabbits. Exp Neurol. 2015;266:143-146. doi: 10.1016/j.expneurol.2015.02.016
  27. Culp WC, Woods SD, Brown AT et al. Three variations in rabbit angiographic stroke models. J Neurosci Methods. 2013;212(2):322-328. doi: 10.1016/j.jneumeth.2012.10.017
  28. Meyer DM, Chen Y, Zivin JA. Dose-finding study of phototherapy on stroke outcome in a rabbit model of ischemic stroke. Neurosci Lett. 2016;630:254-258. doi: 10.1016/j.neulet.2016.06.038
  29. Гусев Е. И., Гехт А. Б. Клинические рекомендации по проведению тромболитической терапии у пациентов с ишемическим инсультом. – М.: Москва, 2015. [Gusev EI, Gekht AB. Klinicheskie rekomendatsii po provedeniyu tromboliticheskoi terapii u patsientov s ishemicheskim insul'tom. Moscow: Moskva; 2015. (In Russ).]
  30. Powers WJ, Rabinstein AA, Ackerson T et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49(3). doi: 10.1161/str.0000000000000158
  31. Feng L, Liu J, Chen J et al. Establishing a model of middle cerebral artery occlusion in rabbits using endovascular interventional techniques. Exp Ther Med. 2013;6(4):947-952. doi: 10.3892/etm.2013.1248
  32. Brown A, Woods S, Skinner R et al. Neurological assessment scores in rabbit embolic stroke models. Open Neurol J. 2013;7(1):38-43. doi: 10.2174/1874205x01307010038
  33. Lapchak P, Boitano P, de Couto G, Marbán E. Intravenous xenogeneic human cardiosphere-derived cell extracellular vesicles (exosomes) improves behavioral function in small-clot embolized rabbits. Exp Neurol. 2018;307:109-117. doi: 10.1016/j.expneurol.2018.06.007
  34. Kawaguchi M, Furuya H. Neuroprotective effects of anesthetic agents. The Journal of Japan Society for Clinical Anesthesia. 2009;29(4):358-363. doi: 10.2199/jjsca.29.358
  35. Jörgensen L, Torvik A. Ischaemic cerebrovascular diseases in an autopsy series Part 2. Prevalence, location, pathogenesis, and clinical course of cerebral infarcts. J Neurol Sci. 1969;9(2):285-320. doi: 10.1016/0022-510x(69)90078-1
  36. Blinc A, Kennedy SD, Bryant RG et al. Flow through clots determines the rate and pattern of fibrinolysis. Thromb Haemost. 1994;71(2):230-235
  37. Kirchhof K, Welzel T, Zoubaa S et al. New method of embolus preparation for standardized embolic stroke in rabbits. Stroke. 2002;33(9):2329-2333. doi: 10.1161/01.str.0000027436.82700.73
  38. Sommer CJ. Ischemic stroke: experimental models and reality. Acta Neuropathol. 2017;133(2):245-261. doi: 10.1007/s00401-017-1667-0
  39. Nagano H, Suzuki T, Hayashi M, Asano M. Cerebral microcirculatory changes after cerebral embolization induced by glass bead injection in rabbits. Angiology. 1992;43(8):678-684. doi: 10.1177/000331979204300808
  40. Winding O. Cerebral microembolization following carotid injection of dextran microspheres in rabbits. Neuroradiology. 1981;21(3):123-126. https://doi.org/10.1007/bf00339519
  41. Molnár L, Hegedüs K, Fekete I. A new model for inducing transient cerebral ischemia and subsequent reperfusion in rabbits without craniectomy. Stroke. 1988;19(10):1262-1266. doi: 10.1161/01.str.19.10.1262
  42. Koizumi J, Yoshida Y, Nishigaya K, Kanai H, Ooneda G. Experimental studies of ischemic brain edema. Effect of recirculation of the blood flow after ischemia on post-ischemic brain edema. Nosotchu. 1989;11(1):11-17. doi: 10.3995/jstroke.11.11
  43. Kong LQ, Xie JX, Han H, Liu HD. Improvements in the intraluminal thread technique to induce focal cerebral ischaemia in rabbits. J Neurosci Methods. 2004;137(2):315-319. doi: 10.1016/j.jneumeth.2004.03.017
  44. Nabavi D, Cenic A, Henderson S et al. Perfusion mapping using computed tomography allows accurate prediction of cerebral infarction in experimental brain ischemia. Stroke. 2001;32(1):175-183. doi: 10.1161/01.str.32.1.175
  45. 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
  46. Macrae IM. Preclinical stroke research – advantages and disadvantages of the most common rodent models of focal ischaemia. Br J Pharmacol. 2011;164(4):1062-1078. doi: 10.1111/j.1476-5381.2011.01398.x
  47. Meyer FB, Anderson RE, Sundt TM, Yaksh TL. Intracellular brain pH, indicator tissue perfusion, electroencephalography, and histology in severe and moderate focal cortical ischemia in the rabbit. Journal of Cerebral Blood Flow & Metabolism. 1986;6(1):71-78. doi: 10.1038/jcbfm.1986.9
  48. Чадаев В. Е. Модельные объекты в медицине и ветеринарии //Вісник проблем біології і медицини. – 2012. – Т. 2. – №. 3. – С.140–145. [Chadaev VE. Model'nye ob»ekty v meditsine i veterinarii. Vіsnik problem bіologії і meditsini. 2012;2(3);140-145. (In Ukrainian).]
  49. Нигматуллин Р. М. Происхождение и генетическая классификация пород кроликов //Вавиловский журнал генетики и селекции. – 2007. – Т. 11. – №. 1. – С. 221-227. [Nigmatullin RM. The origin and genetic classification of rabbit breeds. Russian Journal of Genetics: Applied Research. 2007;11(1):221-227. (In Russ).]
  50. Балакирев Н. А., Нигматуллин Р. М. Межпородная и внутрипородная разнотипичность кроликов и ее роль в селекции //Вавиловский журнал генетики и селекции. – 2014. – Т. 16. – №. 4/2. – С. 1032-1039. [Balakirev NA, Nigmatullin RM. Interbreed and intrabreed variability in rabbits and its role in breeding. Russian Journal of Genetics: Applied Research. 2012;15(4):1032-1039. (In Russ).]
  51. Балакирев Н. А., Нигматуллин Р. М., Сушенцова М. А. Краниологические особенности кроликов разных пород //Ветеринария, зоотехния и биотехнология. – 2017. – №. 7. – С. 38-41. [Balakirev NA, Nigmatullin RM, Sushentsova MA. Craniological peculiarities of different breeds of rabbits. Veterinariya, zootekhniya i biotekhnologiya. 2017;(7):38-41. (In Russ).]
  52. Alkayed NJ, Harukuni I, Kimes AS et al. Gender-linked brain injury in experimental stroke. Stroke. 1998;29(1):159-166. doi: 10.1161/01.str.29.1.159
  53. Физиологические, биохимические и биометрические показатели нормы экспериментальных животных. Справочник. / Под ред. Макарова В.Г., Макаровой М.Н. – СПб.: ЛЕМА, 2013. [Makarov VG, Makarova MN, editors. Fiziologicheskie, biokhimicheskie i biometricheskie pokazateli normy ehksperimental'nykh zhivotnykh. Spravochnik. Saint Petersburg: LEMA; 2013. (In Russ).]
  54. Peeters ME, Gil D, Teske E et al. Four methods for general anaesthesia in the rabbit: a comparative study. Lab Anim. 1988;22(4):355-360. doi: 10.1258/002367788780746197
  55. Flecknell PA, Roughan JV, Hedenqvist P. Induction of anaesthesia with sevoflurane and isoflurane in the rabbit. Lab Anim. 1999;33(1):41-46. doi: 10.1258/002367799780578516
  56. Murthy VS, Zagar ME, Vollmer RR, Schmidt DH. Pentobarbital-induced changes in vagal tone and reflex vagal activity in rabbits. Eur J Pharmacol. 1982;84(1-2):41-50. doi: 10.1016/0014-2999(82)90155-8
  57. Field KJ, White WJ, Lang CM. Anaesthetic effects of chloral hydrate, pentobarbitone and urethane in adult male rats. Lab Anim. 1993;27(3):258-269. doi: 10.1258/002367793780745471
  58. Field KJ, Lang CM. Hazards of urethane (ethyl carbamate): a review of the literature. Lab Anim. 1988;22(3):255-262. doi: 10.1258/002367788780746331
  59. Karasu A, Altuğ N, Aslan L et al. Evaluation of the anesthetic effects of xylazine-ketamine, xylazine-tiletamine-zolazepam and tiletamine-zolazepam using clinical and laboratory parameters in rabbits. Med Weter. 2018;74(10):646-652. doi: 10.21521/mw.6119
  60. Popilskis SJ, Oz MC, Gorman P et al. Comparison of xylazine with tiletamine-zolazepam (Telazol) and xylazine-ketamine anesthesia in rabbits. Lab Anim Sci. 1991;41(1):51-53.
  61. Силачев Д. Н. и др. Влияние наркозных препаратов на эффективность удаленного ишемического прекондиционирования //Биохимия. – 2017. – Т. 82. – №. 9. – С. 1296-1308. [Silachev DN, Usatikova EA, Pevzner IB et al.
  62. Effect of anesthetics on efficiency of remote ischemic preconditioning. Biochemistry (Moscow). 2017;82(9):1296-1308. (In Russ).] https://doi.org/10.1134/S0006297917090036
  63. Li H, Yin J, Li L et al. Isoflurane postconditioning reduces ischemia-induced nuclear factor-κB activation and interleukin 1β production to provide neuroprotection in rats and mice. Neurobiol Dis. 2013;54:216-224. doi: 10.1016/j.nbd.2012.12.014
  64. Brown AT, Skinner RD, Flores R et al. Stroke location and brain function in an embolic rabbit stroke model. Journal of Vascular and Interventional Radiology. 2010;21(6):903-909. doi: 10.1016/j.jvir.2010.02.023
  65. Brown AT, Arthur MC, Nix JS et al. Dodecafluoropentane emulsion (DDFPe) decreases stroke size and improves neurological scores in a permanent occlusion rat stroke model. Open Neurol J. 2014;8(1):27-33. doi: 10.2174/1874205x01408010027
  66. Spilker J, Kongable G, Barch C et al. Using the NIH Stroke Scale to assess stroke patients. The NINDS rt-PA Stroke Study Group. J Neurosci Nurs. 1997;29(6):384-92.
  67. Rasool N, Faroqui M, Rubinstein EH. Lidocaine accelerates neuroelectrical recovery after incomplete global ischemia in rabbits. Stroke. 1990;21(6):929-935. doi: 10.1161/01.str.21.6.929
  68. Lazarewicz JW, Pluta R, Salinska E, Puka M. Beneficial effect of nimodipine on metabolic and functional disturbances in rabbit hippocampus following complete cerebral ischemia. Stroke. 1989;20(1):70-77. doi: 10.1161/01.str.20.1.70
  69. Farias LA, Smith EE, Markov AK. Prevention of ischemic-hypoxic brain injury and death in rabbits with fructose-1,6-diphosphate. Stroke. 1990;21(4):606-613. doi: 10.1161/01.str.21.4.606
  70. Scavini C, Rozza A, Bo P et al. Kappa-opioid receptor changes and neurophysiological alterations during cerebral ischemia in rabbits. Stroke. 1990;21(6):943-947. doi: 10.1161/01.str.21.6.943
  71. Wang DD, Bordey A. The astrocyte odyssey. Prog Neurobiol. 2008. doi: 10.1016/j.pneurobio.2008.09.015
  72. An SA, Kim J, Kim OJ et al. Limited clinical value of multiple blood markers in the diagnosis of ischemic stroke. Clin Biochem. 2013;46(9):710-715. doi: 10.1016/j.clinbiochem.2013.02.005
  73. Zongo D, Ribéreau-Gayon R, Masson F et al. S100-B protein as a screening tool for the early assessment of minor head injury. Ann Emerg Med. 2012;59(3):209-218. doi: 10.1016/j.annemergmed.2011.07.027
  74. González-García S, González-Quevedo A, Fernández-Concepción O et al. Short-term prognostic value of serum neuron specific enolase and S100B in acute stroke patients. Clin Biochem. 2012;45(16-17):1302-1307. doi: 10.1016/j.clinbiochem.2012.07.094
  75. Liu Y, Dargusch R, Maher P, Schubert D. A broadly neuroprotective derivative of curcumin. J Neurochem. 2008;105(4):1336-1345. doi: 10.1111/j.1471-4159.2008.05236.x
  76. Ma L, Harada T, Harada C et al. Neurotrophin-3 is required for appropriate establishment of thalamocortical connections. Neuron. 2002;36(4):623-634. doi: 10.1016/s0896-6273(02)01021-8
  77. Małczyńska P, Piotrowicz Z, Drabarek D, et al. Rola mózgowego czynnika neurotroficznego (BDNF) w procesach neurodegeneracji oraz w mechanizmach neuroregeneracji wywołanej wzmożoną aktywnością fizyczną. Postępy Biochemii. 2019;65(1):2-8. (in Polish). doi: 10.18388/pb.2019_251
  78. Silachev DN, Uchevatkin AA, Pirogov YA, et al. Comparative evaluation of two methods for studies of experimental focal ischemia: magnetic resonance tomography and triphenyltetrazoleum detection of brain injuries. Bull Exp Biol Med. 2009;147(2):269-272. doi: 10.1007/s10517-009-0489-z

Views

Abstract - 112

PDF (Russian) - 60

Cited-By


PlumX

Refbacks

  • There are currently no refbacks.

Copyright (c) 2019 Pharmacy Formulas

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies