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Zalkhani R. Several models of induction seizure and epilepsy in experimental animals. Journal of Research in Applied and Basic Medical Sciences 2020; 6 (4) :252-261
URL: http://ijrabms.umsu.ac.ir/article-1-124-en.html
Ph.D of Physiology, Farhangian University, Tehran, Iran , rahazalkhani@gmail.com
Abstract:   (2248 Views)
Background & Aims:  Animal models provide crucial tools to study epilepsy which is one of the most common   neurological disorder. Experimental models are valid and essential to discover new antiepileptic drugs as well as to elucidate circuitry dysfunction of disease. Therefore, in this review, we summarize the prominent used methods for induction experimental seizures and epilepsy induced by electrical, chemoconvulsants, traumatic brain injury, acoustic stimulation as well as hyperthermia and hypoxia condition.
Material and Methods: In this review data were collected through searching electronic databases of PubMed and Google Scholar for several methods of induction seizure and epilepsy in experimental animals.
Results: The maximal electroshock (MES), pentylentetrazole (PTZ), and 6-Hz seizure models are three simple seizure models for inducing acute seizure in intact animal. The pilocarpine, kainic acid, antibiotics, metals and organophosphorus compounds have epileptogenic potency for inducing motor seizures.
The most common type of chronic models of epilepsy are electrical kindling, PTZ-induced kindling and transgenic models. Pharmacoresistance models include the phenytoin- or lamotrigine-pretreated kindled rats model, the 6-Hz mouse model, pentylentetrazole induced seizures in rats pre-exposed to pilocarpine and intrauterine exposure of rats to methylazoxymethanol. Lastly, Posttraumatic epilepsy, audiogenic seizures, hyperthermia and neonatal hypoxia model as well as in vitro models are used to induce and study seizures.
Conclusion: Epilepsy and seizure in experimental animals can be modeled by several factors include acute and chronic stimulation, mechanical insults and changing environmental conditions in both forms in vivo and vitro.
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Type of Study: review article | Subject: Special

1. Zalkhani R, Moazedi A. Basic and clinical role of vitamins in epilepsy. RABMS 2020 ;10;6(2):104-14. [Google Scholar]
2. Loscher W, Brandt C. Prevention or modification of epileptogenesis after brain insults: experimental approaches and translational research. Pharmacol Rev 2010;62(4):668-700. [DOI:10.1124/pr.110.003046] [PMID] [PMCID]
3. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel Jr J, Forsgren L, French JA, Glynn M, Hesdorffer DC. ILAE official report: a practical clinical definition of epilepsy. Epilepsia 2014;55(4):475-82. [DOI:10.1111/epi.12550] [PMID]
4. Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, Shorvon S, Lowenstein DH. A definition and classification of status epilepticus-Report of the ILAE task force on classification of status epilepticus. Epilepsia 2015;56(10):1515-23. [DOI:10.1111/epi.13121] [PMID]
5. Robertshawe P. Pizzorno JE, Murray MT, Joiner-Bey H. The clinician's handbook of natural medicine. J AUST TRADIT-MED SO 2009;15(4):244-5. [Google Scholar]
6. Pack AM. Epilepsy overview and revised classification of seizures and epilepsies. Continuum (Minneap Minn) 2019;25(2):306-21. [DOI:10.1212/CON.0000000000000707] [PMID]
7. Nordli Jr DR. Focal and multifocal seizures. In Swaiman's pediatric neurology. Elsevier 2017; 531-537. [DOI:10.1016/B978-0-323-37101-8.00067-9]
8. Giardina WJ. Models of epilepsy: electroshock and chemical induced convulsions in the mouse. Animals models of disease. Curr Protoc Pharmacol 2000;1: 5.22.1-5.22.22. [DOI:10.1002/0471141755.ph0522s10]
9. Abend NS, Jensen FE, Inder TE, Volpe JJ. Neonatal seizures. In Volpe's neurology of the newborn. Elsevier 2018; 275-321. [DOI:10.1016/B978-0-323-42876-7.00012-0]
10. Sirven JI. Epilepsy: a spectrum disorder. CSH PERSPECT MED 2015;5(9): a022848. [DOI:10.1101/cshperspect.a022848] [PMID] [PMCID]
11. Stafstrom CE, Carmant L. Seizures and epilepsy: an overview for neuroscientists. CSH PERSPECT MED 2015;5(6): a022426. [DOI:10.1101/cshperspect.a022426] [PMID] [PMCID]
12. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas Wet al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 2010;51(4):676-85. [DOI:10.1111/j.1528-1167.2010.02522.x] [PMID]
13. Loscher W. Animal models of seizures and epilepsy: past, present, and future role for the discovery of antiseizure drugs. Neurochem. Res 2017;42(7):1873-88. [DOI:10.1007/s11064-017-2222-z] [PMID]
14. Löscher W. Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs. Seizure 2011;20(5):359-68. [DOI:10.1016/j.seizure.2011.01.003] [PMID]
15. Toman JEP, Swinyard EA, Goodman LS. Properties of maximal seizures and their alteration by anticonvulsant drugs and other agents. J Neurophysiol 1964; 9:231-9. [DOI:10.1152/jn.1946.9.3.231] [PMID]
16. Heuzeroth H, Wawra M, Fidzinski P, Dag R, Holtkamp M. The 4-aminopyridine model of acute seizures in vitro elucidates efficacy of new antiepileptic drugs. Front Neurosci-Switz 2019; 13:677. [DOI:10.3389/fnins.2019.00677] [PMID] [PMCID]
17. Kandratavicius L, Balista PA, Lopes-Aguiar C, Ruggiero RN, Umeoka EH, Garcia-Cairasco N. Animal models of epilepsy: use and limitations. Neuropsych Dis Treat 2014: 1693-705. [DOI:10.2147/NDT.S50371] [PMID] [PMCID]
18. Loscher W, Schmidt D. Which animal models should be used in the search for new antiepileptic drugs? A proposal based on experimental and clinical considerations. Epilepsy Res. 1988;2(3):145-81. [DOI:10.1016/0920-1211(88)90054-X]
19. Suhasini GE, Giri A. Maximal electroshock (MES) induced convulsions model for evaluating anti-epileptic activity of new is at in derivative-N'-(7-Chloro-2-Oxo-2, 3-Dihydro-1H-Indol-3-yl) Benzohydrazide. Int. J. Res 2014;5(4):328-33. [Google Scholar]
20. Pitkänen A, Buckmaster P, Galanopoulou AS, Moshé SL, editors. Models of seizures and epilepsy. Academic Press; 2017. P.127-50. [Google Scholar]
21. Cavarsan CF, Matsuo A, Blanco MM, Mello LE. Maximal electroshock-induced seizures are able to induce Homer1a mRNA expression but not pentylenetetrazole-induced seizures. Epilepsy Behav 2015;44:90-5. [DOI:10.1016/j.yebeh.2014.12.034] [PMID]
22. Löscher W, Schmidt D. Modern antiepileptic drug development has failed to deliver: ways out of the current dilemma. Epilepsia 2011;52(4):657-78. [DOI:10.1111/j.1528-1167.2011.03024.x] [PMID]
23. VELÍŠEK L. Models of chemically-induced acute seizures. Models of seizures and epilepsy 2006;127-52. [DOI:10.1016/B978-012088554-1/50013-X]
24. Miller JW, McKeon AC, Ferrendelli JA. Functional anatomy of pentylenetetrazol and electroshock seizures in the rat brainstem. Ann Neurol: Official journal of the american neurological association and the child neurology society 1987;22(5):615-21. [DOI:10.1002/ana.410220510] [PMID]
25. White HS, Johnson M, Wolf HH, Kupferberg HJ. The early identification of anticonvulsant activity: role of the maximal electroshock and subcutaneous pentylenetetrazol seizure models. Ital J Neurol Sci 1995;16(1-2):73-7. [DOI:10.1007/BF02229077] [PMID]
26. Mandhane SN, Aavula K, Rajamannar T. Timed pentylenetetrazol infusion test: a comparative analysis with sc PTZ and MES models of anticonvulsant screening in mice. Seizure 2007;16(7):636-44. [DOI:10.1016/j.seizure.2007.05.005] [PMID]
27. Daneshkhah M, Setorki M. Protective effects of artemisia persica essential oil against pentylenetetrazol-induced seizure in male mice with emphasizing its mechanism of action. Iran. Red Crescent Med J 2019;21(2). [DOI:10.5812/ircmj.85021]
28. Kline KL. Seizure Disorders and Treatment Options. Consultations in feline internal medicine 2009; 517-526. [DOI:10.1016/B0-72-160423-4/50058-5] [PMCID]
29. Van Erum J, Van Dam D, De Deyn PP. PTZ-induced seizures in mice require a revised Racine scale. Epilepsy Behav 2019;95:51-5. [DOI:10.1016/j.yebeh.2019.02.029] [PMID]
30. Scorza FA, Arida RM, Naffah-Mazzacoratti MD, Scerni DA, Calderazzo L, Cavalheiro EA. The pilocarpine model of epilepsy: what have we learned? An Acad Bras 2009;81(3):345-65. [DOI:10.1590/S0001-37652009000300003] [PMID]
31. Curia G, Longo D, Biagini G, Jones RS, Avoli M. The pilocarpine model of temporal lobe epilepsy. J Neurosci Methods 2008;172(2):143-57. [DOI:10.1016/j.jneumeth.2008.04.019] [PMID] [PMCID]
32. Turski WA, Cavalheiro EA, Schwarz M, Czuczwar SJ, Kleinrok Z, Turski L. Limbic seizures produced by pilocarpine in rats: behavioural, electroencephalographic and neuropathological study. Behav. Brain Res 1983;9(3):315-35. [DOI:10.1016/0166-4328(83)90136-5]
33. Shinozaki H, Konishi S. Actions of several anthelmintics and insecticides on rat cortical neurones. Brain Res 1970;24(2):368-71. [DOI:10.1016/0006-8993(70)90122-8]
34. Levesque M, Avoli M. The kainic acid model of temporal lobe epilepsy. Neurosci Biobehav Rev 2013;37(10):2887-99. [DOI:10.1016/j.neubiorev.2013.10.011] [PMID] [PMCID]
35. Jasper H, Cone W, Pudenz R, Bennett T. The electroencephalograms of monkeys following the application of microcrystalline sulfonamides to the brain. Surg Gynecol Obstet 1943;76:599-611. [Google Scholar]
36. Bauquier SH, Jiang JL, Lai A, Cook MJ. Clonic seizures in GAERS rats after oral administration of enrofloxacin. Comp. Med 2016;66(3):220-4. [Google Scholar]
37. Antoniadis A, Müller WE, Wollert U. Inhibition of GABA and benzodiazepine receptor binding by penicillins. Neurosci. Lett 1980;18(3):309-12. [DOI:10.1016/0304-3940(80)90302-X]
38. Akdogan I, Adiguzel E, Yilmaz I, Ozdemir MB, Sahiner M, Tufan AC. Penicillin-induced epilepsy model in rats: dose-dependant effect on hippocampal volume and neuron number. Brain Res Bull 2008;77(4):172-7. [DOI:10.1016/j.brainresbull.2008.08.001] [PMID]
39. Ayyıldız M, Yıldırım M, Agar E. The effects of vitamin E on penicillin-induced epileptiform activity in rats. Exp. Brain Res 2006;174(1):109-13. [DOI:10.1007/s00221-006-0425-7] [PMID]
40. Grondahl To, Langmoen IA. Epileptogenic effect of antibiotic drugs. J Neurosurg 1993;78(6):938-43. [DOI:10.3171/jns.1993.78.6.0938] [PMID]
41. Sharma V, Babu PP, Singh A, Singh S, Singh R. Iron-induced experimental cortical seizures: electroencephalographic mapping of seizure spread in the subcortical brain areas. Seizure 2007;16(8):680-90. [DOI:10.1016/j.seizure.2007.05.012] [PMID]
42. Pereira EF, Aracava Y, DeTolla LJ, Beecham EJ, Basinger GW, Wakayama EJ, Albuquerque EX. Animal models that best reproduce the clinical manifestations of human intoxication with organophosphorus compounds. J Pharmacol Exp 2014;350(2):313-21. [DOI:10.1124/jpet.114.214932] [PMID] [PMCID]
43. Lorke DE, Petroianu GA. Reversible cholinesterase inhibitors as pretreatment for exposure to organophosphates. A review. J Appl Toxicol 2019;39(1):101-16. [DOI:10.1002/jat.3662] [PMID]
44. McNamara JO. Kindling: an animal model of complex partial epilepsy. Ann Neurol : official journal of the american neurological association and the child neurology society. 1984;16(S1):S72-6. [DOI:10.1002/ana.410160712] [PMID]
45. Zalkhani R, Moazedi AA, Ghotbeddin Z, Borujeni MP. The therapeutic effects of low-frequency electrical stimulations adjunct to sodium valproate on seizure and behaviors. BCN 2020;11(1):59. [Google Scholar]
46. White HS. Animal models for evaluating antiepileptogenesis. Epilepsia 2010 Dec; 51:87-87. [DOI:10.1111/j.1528-1167.2010.02873.x]
47. Morales JC, Álvarez-Ferradas C, Roncagliolo M, Fuenzalida M, Wellmann M, Nualart FJ, Bonansco C. A new rapid kindling variant for induction of cortical epileptogenesis in freely moving rats. Front Cell Neurosci 2014 ;23;8:200. [DOI:10.3389/fncel.2014.00200]
48. Rajabzadeh A, Bideskan AE, Fazel A, Sankian M, Rafatpanah H, Haghir H. The effect of PTZ-induced epileptic seizures on hippocampal expression of PSA-NCAM in offspring born to kindled rats. J. Biomed Sci 2012;19(1):1-9. [DOI:10.1186/1423-0127-19-56] [PMID] [PMCID]
49. Serikawa T, Mashimo T, Kuramoto T, Voigt B, Ohno Y, Sasa M. Advances on genetic rat models of epilepsy. Exp Anim 2014:14-0066. [Google Scholar]
50. Stables JP, Bertram E, Dudek FE, Holmes G, Mathern G, Pitkanen A, White HS. Therapy discovery for pharmacoresistant epilepsy and for disease‐modifying therapeutics: summary of the NIH/NINDS/AES models II workshop. Epilepsia 2003;44(12):1472-8. [DOI:10.1111/j.0013-9580.2003.32803.x] [PMID]
51. Potschka H. Animal models of drug-resistant epilepsy. Epileptic Disord 2012 ;14(3):226-34. [DOI:10.1684/epd.2012.0532] [PMID]
52. Farber NB, Jiang XP, Heinkel C, Nemmers B. Antiepileptic drugs and agents that inhibit voltage-gated sodium channels prevent NMDA antagonist neurotoxicity. Mol Psychiatry 2002;7(7):726-33. [DOI:10.1038/sj.mp.4001087] [PMID]
53. Mousavi-Hasanzadeh M, Rezaeian-Varmaziar H, Shafaat O, Jand A, Palizvan MR. The effect of co-administration of pentylenetetrazole with pilocarpine: New modified PTZ models of kindling and seizure. Pharmacol Biochem Behav 2019;182:7-11. [DOI:10.1016/j.pbb.2019.04.010] [PMID]
54. Santos AC, Temp FR, Marafiga JR, Pillat MM, Hessel AT, Ribeiro LR, Miyazato LG, Oliveira MS, Mello CF. EP2 receptor agonist ONO-AE1-259-01 attenuates pentylenetetrazole-and pilocarpine-induced seizures but causes hippocampal neurotoxicity. Epilepsy Behav 2017;73:180-8. [DOI:10.1016/j.yebeh.2017.03.033] [PMID]
55. Hartman AL, Lyle M, Rogawski MA, Gasior M. Efficacy of the ketogenic diet in the 6‐Hz seizure test. Epilepsia 2008;49(2):334-9. [DOI:10.1111/j.1528-1167.2007.01430.x] [PMID] [PMCID]
56. Giordano C, Vinet J, Curia G, Biagini G. Repeated 6-Hz corneal stimulation progressively increases FosB/ΔFosB levels in the lateral amygdala and induces seizure generalization to the hippocampus. PloS one 2015;10(11):e0141221. [DOI:10.1371/journal.pone.0141221] [PMID] [PMCID]
57. Metcalf CS, West PJ, Thomson KE, Edwards SF, Smith MD, White HS, et al. Development and pharmacologic characterization of the rat 6 Hz model of partial seizures. Epilepsia 2017;58(6):1073-84. [DOI:10.1111/epi.13764] [PMID] [PMCID]
58. Smyth MD, Barbaro NM, Baraban SC. Effects of antiepileptic drugs on induced epileptiform activity in a rat model of dysplasia. Epilepsy Res 2002;50(3):251-64. [DOI:10.1016/S0920-1211(02)00051-7]
59. Dutertre S, Becker CM, Betz H. Inhibitory glycine receptors: an update. J Biol 2012;287(48):40216-23. [DOI:10.1074/jbc.R112.408229] [PMID] [PMCID]
60. Zalkhani R, Moazed AA, Najafzadehvarzi H. Therapeutic effects of combination of sodium valproate and vitamin C and E on seizure induced by strychnine in adult rat. JSUMS 2019:2:195-201. [Google Scholar]
61. Brady RD, Casillas-Espinosa PM, Agoston DV, Bertram EH, Kamnaksh A, Semple BD, Shultz SR. Modelling traumatic brain injury and posttraumatic epilepsy in rodents. Neurobiol Dis 2019;123:8-19. [DOI:10.1016/j.nbd.2018.08.007] [PMID] [PMCID]
62. Kabadi SV, Hilton GD, Stoica BA, Zapple DN, Faden AI. Fluid-percussion-induced traumatic brain injury model in rats. Nat. Protoc. 2010;5(9):1552. [DOI:10.1038/nprot.2010.112] [PMID] [PMCID]
63. Osier ND, Dixon CE. The controlled cortical impact model: applications, considerations for researchers, and future directions. Front Neurol 2016;7:134. [DOI:10.3389/fneur.2016.00134] [PMID] [PMCID]
64. Mychasiuk R, Hehar H, Candy S, Ma I, Esser MJ. The direction of the acceleration and rotational forces associated with mild traumatic brain injury in rodent's effect behavioural and molecular outcomes. J. Neurosci. Methods. 2016;257:168-78. [DOI:10.1016/j.jneumeth.2015.10.002] [PMID]
65. Ling G, Bandak F, Armonda R, Grant G, Ecklund J. Explosive blast neurotrauma. J Neurotrauma 2009;26(6):815-25. [DOI:10.1089/neu.2007.0484] [PMID]
66. Williams AJ, Hartings JA, Lu XC, Rolli ML, Dave JR, Tortella FC. Characterization of a new rat model of penetrating ballistic brain injury. J Neurotrauma 2005;22(2):313-31. [DOI:10.1089/neu.2005.22.313] [PMID]
67. Newton J, N'Gouemo P. Withdrawal seizures. In models of seizures and epilepsy. Academic Press; 2017. P. 911-31. [DOI:10.1016/B978-0-12-804066-9.00062-6]
68. Jensen FE, Blume H, Alvarado S, Firkusny I, Geary C. NBQX blocks acute and late epileptogenic effects of perinatal hypoxia. Epilepsia 1995;36(10):966-72. [DOI:10.1111/j.1528-1157.1995.tb00954.x] [PMID]
69. Stasheff SF, Bragdon AC, Wilson WA. Induction of epileptiform activity in hippocampal slices by trains of electrical stimuli. Brain Res 1985;344(2):296-302. [DOI:10.1016/0006-8993(85)90807-8]
70. Tancredi V, Hwa GG, Zona C, Brancati A, Avoli M. Low magnesium epileptogenesis in the rat hippocampal slice: electrophysiological and pharmacological features. Brain Res 1990;511(2):280-90. [DOI:10.1016/0006-8993(90)90173-9]
71. Chesnut TJ, Swann JW. Epileptiform activity induced by 4-aminopyridine in immature hippocampus. Epilepsy Res 1988;2(3):187-95. [DOI:10.1016/0920-1211(88)90056-3]

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