颞叶癫痫动物模型_Journal of Epilepsy

Authors：

 朱飞 ^1,2,3 , 郎森阳 ⁴ ,  王群 ^1,2,3

1. ;
2. ;
3. ;
4. ;

Corresponding author：

王群, Email: wangq@ccmu.edu.cn

Keywords：

颞叶癫痫; 海马; 海人酸; 匹罗卡品; 动物模型

DOI：

10.7507/2096-0247.20160029

Video：

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癫痫是一种神经系统常见疾病，绝大多数癫痫患者可以通过药物控制发作，但是仍有约1/3患者为药物难治性癫痫，在难治性癫痫中绝大多数为颞叶癫痫。对颞叶癫痫动物模型的研究有助于了解其发病机制、脑电改变及病理生理特点，为寻找其治疗方法有一定帮助。现就颞叶癫痫动物模型的制作方法、行为学表现、脑电改变及病理特征进行总结。目前常用颞叶癫痫动物模型有海人酸模型和匹罗卡品模型，两种模型均可以通过系统给药和局部给药方式实现，可以诱发急性癫痫持续状态，之后出现反复自发发作从而形成慢性癫痫模型。两种模型均可引发海马起源的痫样放电，造成海马神经元变性、胶质细胞增生及苔藓纤维出芽，与人类颞叶癫痫相似。

Citation： 朱飞, 郎森阳, 王群. 颞叶癫痫动物模型. Journal of Epilepsy, 2016, 2(2): 151-154. doi: 10.7507/2096-0247.20160029 Copy

1.	Sander JW. The epidemiology of epilepsy revisited. Curr Opin Neurol, 2003,16(2): 165-170.
2.	Kwan P,Sander JW.The natural history of epilepsy: an epidemiological view. J Neurol Neurosurg Psychiatry, 2004,75(10): 1376-1381.
3.	Engel J Jr. Clinical neurophysiology, neuroimaging and the surgical treatment of epilepsy. Curr Opin Neurol Neurosurg, 1993, 6(2): 240-249.
4.	Engel J Jr, Dermott MP Mc, Wiebe S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA, 2012, 307(9): 922-930.
5.	Schmidt D, Loscher W. Drug resistance in epilepsy: putative neurobiologic and clinical mechanisms. Epilepsia, 2005, 46(6): 858-877.
6.	Engel J Jr. Mesial temporal lobe epilepsy: what have we learned? Neuroscientist, 2001, 7(4): 340-352.
7.	Andres-Mach M, Fike JR, Luszczki JJ. Neurogenesis in the epileptic brain: a brief overview from temporal lobe epilepsy. Pharmacol Rep, 2011. 63(6): 1316-1323.
8.	Ben-Ari Y, Crepel V, Represa A. Seizures beget seizures in temporal lobe epilepsies: the boomerang effects of newly formed aberrant kainatergic synapses. Epilepsy Curr, 2008, 8(3): 68-72.
9.	Kandratavicius L, Balista PA, Lopes-Aguiar C, et al. Animal models of epilepsy: use and limitations. Neuropsychiatr Dis Treat, 2014, 10(9): 1693-1705.
10.	Babb TL. Synaptic reorganizations in human and rat hippocampal epilepsy. Adv Neurol, 1999, 79: 763-779.
11.	Levesque M, Avoli M. The kainic acid model of temporal lobe epilepsy. Neurosci Biobehav Rev, 2013, 37(10 Pt 2): 2887-2899.
12.	Cendes F. Progressive hippocampal and extrahippocampal atrophy in drug resistant epilepsy. Curr Opin Neurol, 2005, 18(2): 173-177.
13.	Cavalheiro EA. The pilocarpine model of epilepsy. Ital J Neurol Sci, 1995, 16(1-2): 33-37.
14.	Jefferys J, Steinhauser C, Bedner P. Chemically-induced TLE models: Topical application. J Neurosci Methods, 2015, 8(5): S0165-0270.
15.	Sloviter RS. The neurobiology of temporal lobe epilepsy: too much information, not enough knowledge. C R Biol, 2005,328(2): 143-153.
16.	Shibley H, Smith BN. Pilocarpine-induced status epilepticus results in mossy fiber sprouting and spontaneous seizures in C57BL/6 and CD-1 mice. Epilepsy Res, 2002, 49(2): 109-120.
17.	Turski WA, Cavalheiro EA, Bortolotto ZA, et al. Seizures produced by pilocarpine in mice: a behavioral, electroencephalographic and morphological analysis. Brain Res, 1984, 321(2): 237-253.
18.	Tsai CY, Chan JY, Hsu KS, et al. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus. PLoS One, 2012, 7(3): e33527.
19.	Isaev D, Zhao Q, Kleen JK, et al. Neuroaminidase reduces interictal spikes in a rat temporal lobe epilepsy model. Epilepsia, 2011, 52(3): e12-15.
20.	Cavalheiro EA, Leite JP, Bortolotto ZA, et al. Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia, 1991, 32(6): 778-782.
21.	Ben-Ari Y, Lagowska J. Epileptogenic action of intra-amygdaloid injection of kainic acid. C R Acad Sci Hebd Seances Acad Sci D, 1978, 287(8): 813-816.
22.	Ben-Ari Y, Lagowska J, Tremblay E, et al. A new model of focal status epilepticus: intra-amygdaloid application of kainic acid elicits repetitive secondarily generalized convulsive seizures. Brain Res, 1979, 163(1): 176-179.
23.	Inostroza M, Cid E, Menendez de la Prida L, et al. Different emotional disturbances in two experimental models of temporal lobe epilepsy in rats. Plos One, 2012, 7(6): e38959.
24.	Bragin A, Engel Jr J, Wilson CL, et al. Electrophysiologic analysis of a chronic seizure model after unilateral hippocampal KA injection. Epilepsia, 1999, 40(9): 1210-1221.
25.	Bragin A, Wilson CL, Engel Jr J. Chronic epileptogenesis requires development of a network of pathologically interconnected neuron clusters: a hypothesis. Epilepsia, 2000, 41 (Suppl 6): 144-152.
26.	Bragin A, Wilson CL, Almajano J, et al. High-frequency oscillations after status epilepticus: epileptogenesis and seizure genesis. Epilepsia, 2004, 45(9): 1017-1023.
27.	Bragin A, Azizyan A, Almajano J, et al. The cause of the imbalance in the neuronal network leading to seizure activity can be predicted by the electrographic pattern of the seizure onset. J Neurosci, 2009, 29(11): 3660-3671.
28.	Carriero G, Arcieri S, Cattalini A, et al. A guinea pig model of mesial temporal lobe epilepsy following nonconvulsive status epilepticus induced by unilateral intrahippocampal injection of kainic acid. Epilepsia, 2012, 53(11): 1917-1927.
29.	Raedt R, Van Dycke A, Van Melkebeke D, et al. Seizures in the intrahippocampal kainic acid epilepsy model: characterization using long-term video-EEG monitoring in the rat. Acta Neurol Scand, 2009, 119(5): 293-303.
30.	Skucas VA, Duffy AM, Harte-Hargrove LC, et al. Testosterone depletion in adult male rats increases mossy fiber transmission, LTP, and sprouting in area CA3 of hippocampus. J Neurosci, 2013, 33(6): 2338-2355.
31.	Racine RJ. Modification of seizure activity by electrical stimulation II motor seizure. Electroencephalogr Clin Neurophysiol, 1972, 32(3): 281-294.
32.	Mouri G, Jimenez-Mateos E, Engel T, et al. Unilateral hippocampal CA3-predominant damage and short latency epileptogenesis after intra-amygdala microinjection of kainic acid in mice. Brain Res, 2008, 1213(1): 140-151.
33.	Pernot F, Heinrich C, Barbier L, et al. Inflammatory changes during epileptogenesis and spontaneous seizures in a mouse model of mesiotemporal lobe epilepsy. Epilepsia, 2011, 52(12): 2315-2325.
34.	Leite JP, Babb TL, Pretorius JK, et al. Neuron loss, mossy fiber sprouting, and interictal spikes after intrahippocampal kainate in developing rats. Epilepsy Res, 1996, 26(1): 219-231.
35.	Longo BM, Mello LE. Effect of long-t spontaneous recurrent seizures or reinduction of status epilepticus on the development of supragranular mossy fiber sprouting. Epilepsy Res, 1999, 36(2-3): 233-241.
36.	Riban V, Bouilleret V, Pham-Le BT, et al. Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy. Neuroscience, 2002, 112(1): 101-111.
37.	Lancaster B, Wheal HV. A comparative histological and electrophysiological study of some neurotoxins in the rat hippocampus. J Comp Neurol, 1982, 211(2): 105-114.
38.	Nadler JV, Cuthbertson GJ. Kainic acid neurotoxicity toward hippocampal formation: dependence on specific excitatory pathways. Brain Res, 1980, 195(1): 47-56.
39.	Ben-Ari Y, Tremblay E, Ottersen OP, et al. The role of epileptic activity in hippocampal and “remote” cerebral lesions induced by kainic acid. Brain Res, 1980, 191(1): 79-97.
40.	Tang FR, Loke WK. Cyto- axo- and dendro-architectonic changes of neurons in the limbic system in the mouse pilocarpine model of temporal lobe epilepsy. Epilepsy Res, 2010, 89(1): 43-51.
41.	Bortel A, Levesque M, Biagini G, et al. Convulsive status epilepticus duration as determinant for epileptogenesis and interictal discharge generation in the rat limbic system. Neurobiol Dis, 2010, 40(2): 478-489.
42.	Levesque M, Bortel A, Gotman J, et al. High-frequency (80-500 Hz) oscillations and epileptogenesis in temporal lobe epilepsy. Neurobiol Dis, 2011, 42(3): 231-241.
43.	Kleen JK, Scott RC, Holmes GL, et al. Hippocampal interictal spikes disrupt cognition in rats. Ann Neurol, 2010, 67(2): 250-257.
44.	Scorza FA, Arida RM, Naffah-Mazzacoratti Mda G, et al. The pilocarpine model of epilepsy: what have we learned?. An Acad Bras Cienc, 2009, 81(3): 345-365.
45.	Arida RM, Scorza FA, Peres CA, et al. The course of untreated seizures in the pilocarpine model of epilepsy. Epilepsy Res, 1999, 34(2-3): 99-107.
46.	Curia G, Longo D, Biagini G, et al. The pilocarpine model of temporal lobe epilepsy. J Neurosci Methods, 2008, 172(2): 143-157.
47.	Priel MR, dos Santos NF, Cavalheiro EA. Developmental aspects of the pilocarpine model of epilepsy. Epilepsy Res, 1996, 26(1): 115-121.
48.	Leite JP, Bortolotto ZA, Cavalheiro EA. Spontaneous recurrent seizures in rats: an experimental model of partial epilepsy. Neurosci Biobehav Rev, 1990, 14(4): 511-517.
49.	Furtado Mde A, Braga GK, Oliveira JA, et al. Behavioral, morphologic, and electroencephalographic evaluation of seizures induced by intrahippocampal microinjection of pilocarpine. Epilepsia, 2002, 43 (Suppl 5): 37-39.
50.	Pitkanen A, Sutula TP. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol, 2002, 1(3): 173-181.
51.	Cavazos JE, Das I, Sutula TP. Neuronal loss induced in limbic pathways by kindling: evidence for induction of hippocampal sclerosis by repeated brief seizures. J Neurosci, 1994, 14(5 Pt 2): 3106-3121.
52.	Gorter JA, van Vliet EA, Lopes da Silva FH. Which insights have we gained from the kindling and post-status epilepticus models? J Neurosci Methods, 2015, 4(1): S0165-0270.
53.	Sharma AK, Reams RY, Jordan WH, et al. Mesial temporal lobe epilepsy: pathogenesis, induced rodent models and lesions. Toxicol Pathol, 2007,35(7): 984-999.

1. Sander JW. The epidemiology of epilepsy revisited. Curr Opin Neurol, 2003,16(2): 165-170.
2. Kwan P,Sander JW.The natural history of epilepsy: an epidemiological view. J Neurol Neurosurg Psychiatry, 2004,75(10): 1376-1381.
3. Engel J Jr. Clinical neurophysiology, neuroimaging and the surgical treatment of epilepsy. Curr Opin Neurol Neurosurg, 1993, 6(2): 240-249.
4. Engel J Jr, Dermott MP Mc, Wiebe S, et al. Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. JAMA, 2012, 307(9): 922-930.
5. Schmidt D, Loscher W. Drug resistance in epilepsy: putative neurobiologic and clinical mechanisms. Epilepsia, 2005, 46(6): 858-877.
6. Engel J Jr. Mesial temporal lobe epilepsy: what have we learned? Neuroscientist, 2001, 7(4): 340-352.
7. Andres-Mach M, Fike JR, Luszczki JJ. Neurogenesis in the epileptic brain: a brief overview from temporal lobe epilepsy. Pharmacol Rep, 2011. 63(6): 1316-1323.
8. Ben-Ari Y, Crepel V, Represa A. Seizures beget seizures in temporal lobe epilepsies: the boomerang effects of newly formed aberrant kainatergic synapses. Epilepsy Curr, 2008, 8(3): 68-72.
9. Kandratavicius L, Balista PA, Lopes-Aguiar C, et al. Animal models of epilepsy: use and limitations. Neuropsychiatr Dis Treat, 2014, 10(9): 1693-1705.
10. Babb TL. Synaptic reorganizations in human and rat hippocampal epilepsy. Adv Neurol, 1999, 79: 763-779.
11. Levesque M, Avoli M. The kainic acid model of temporal lobe epilepsy. Neurosci Biobehav Rev, 2013, 37(10 Pt 2): 2887-2899.
12. Cendes F. Progressive hippocampal and extrahippocampal atrophy in drug resistant epilepsy. Curr Opin Neurol, 2005, 18(2): 173-177.
13. Cavalheiro EA. The pilocarpine model of epilepsy. Ital J Neurol Sci, 1995, 16(1-2): 33-37.
14. Jefferys J, Steinhauser C, Bedner P. Chemically-induced TLE models: Topical application. J Neurosci Methods, 2015, 8(5): S0165-0270.
15. Sloviter RS. The neurobiology of temporal lobe epilepsy: too much information, not enough knowledge. C R Biol, 2005,328(2): 143-153.
16. Shibley H, Smith BN. Pilocarpine-induced status epilepticus results in mossy fiber sprouting and spontaneous seizures in C57BL/6 and CD-1 mice. Epilepsy Res, 2002, 49(2): 109-120.
17. Turski WA, Cavalheiro EA, Bortolotto ZA, et al. Seizures produced by pilocarpine in mice: a behavioral, electroencephalographic and morphological analysis. Brain Res, 1984, 321(2): 237-253.
18. Tsai CY, Chan JY, Hsu KS, et al. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus. PLoS One, 2012, 7(3): e33527.
19. Isaev D, Zhao Q, Kleen JK, et al. Neuroaminidase reduces interictal spikes in a rat temporal lobe epilepsy model. Epilepsia, 2011, 52(3): e12-15.
20. Cavalheiro EA, Leite JP, Bortolotto ZA, et al. Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia, 1991, 32(6): 778-782.
21. Ben-Ari Y, Lagowska J. Epileptogenic action of intra-amygdaloid injection of kainic acid. C R Acad Sci Hebd Seances Acad Sci D, 1978, 287(8): 813-816.
22. Ben-Ari Y, Lagowska J, Tremblay E, et al. A new model of focal status epilepticus: intra-amygdaloid application of kainic acid elicits repetitive secondarily generalized convulsive seizures. Brain Res, 1979, 163(1): 176-179.
23. Inostroza M, Cid E, Menendez de la Prida L, et al. Different emotional disturbances in two experimental models of temporal lobe epilepsy in rats. Plos One, 2012, 7(6): e38959.
24. Bragin A, Engel Jr J, Wilson CL, et al. Electrophysiologic analysis of a chronic seizure model after unilateral hippocampal KA injection. Epilepsia, 1999, 40(9): 1210-1221.
25. Bragin A, Wilson CL, Engel Jr J. Chronic epileptogenesis requires development of a network of pathologically interconnected neuron clusters: a hypothesis. Epilepsia, 2000, 41 (Suppl 6): 144-152.
26. Bragin A, Wilson CL, Almajano J, et al. High-frequency oscillations after status epilepticus: epileptogenesis and seizure genesis. Epilepsia, 2004, 45(9): 1017-1023.
27. Bragin A, Azizyan A, Almajano J, et al. The cause of the imbalance in the neuronal network leading to seizure activity can be predicted by the electrographic pattern of the seizure onset. J Neurosci, 2009, 29(11): 3660-3671.
28. Carriero G, Arcieri S, Cattalini A, et al. A guinea pig model of mesial temporal lobe epilepsy following nonconvulsive status epilepticus induced by unilateral intrahippocampal injection of kainic acid. Epilepsia, 2012, 53(11): 1917-1927.
29. Raedt R, Van Dycke A, Van Melkebeke D, et al. Seizures in the intrahippocampal kainic acid epilepsy model: characterization using long-term video-EEG monitoring in the rat. Acta Neurol Scand, 2009, 119(5): 293-303.
30. Skucas VA, Duffy AM, Harte-Hargrove LC, et al. Testosterone depletion in adult male rats increases mossy fiber transmission, LTP, and sprouting in area CA3 of hippocampus. J Neurosci, 2013, 33(6): 2338-2355.
31. Racine RJ. Modification of seizure activity by electrical stimulation II motor seizure. Electroencephalogr Clin Neurophysiol, 1972, 32(3): 281-294.
32. Mouri G, Jimenez-Mateos E, Engel T, et al. Unilateral hippocampal CA3-predominant damage and short latency epileptogenesis after intra-amygdala microinjection of kainic acid in mice. Brain Res, 2008, 1213(1): 140-151.
33. Pernot F, Heinrich C, Barbier L, et al. Inflammatory changes during epileptogenesis and spontaneous seizures in a mouse model of mesiotemporal lobe epilepsy. Epilepsia, 2011, 52(12): 2315-2325.
34. Leite JP, Babb TL, Pretorius JK, et al. Neuron loss, mossy fiber sprouting, and interictal spikes after intrahippocampal kainate in developing rats. Epilepsy Res, 1996, 26(1): 219-231.
35. Longo BM, Mello LE. Effect of long-t spontaneous recurrent seizures or reinduction of status epilepticus on the development of supragranular mossy fiber sprouting. Epilepsy Res, 1999, 36(2-3): 233-241.
36. Riban V, Bouilleret V, Pham-Le BT, et al. Evolution of hippocampal epileptic activity during the development of hippocampal sclerosis in a mouse model of temporal lobe epilepsy. Neuroscience, 2002, 112(1): 101-111.
37. Lancaster B, Wheal HV. A comparative histological and electrophysiological study of some neurotoxins in the rat hippocampus. J Comp Neurol, 1982, 211(2): 105-114.
38. Nadler JV, Cuthbertson GJ. Kainic acid neurotoxicity toward hippocampal formation: dependence on specific excitatory pathways. Brain Res, 1980, 195(1): 47-56.
39. Ben-Ari Y, Tremblay E, Ottersen OP, et al. The role of epileptic activity in hippocampal and “remote” cerebral lesions induced by kainic acid. Brain Res, 1980, 191(1): 79-97.
40. Tang FR, Loke WK. Cyto- axo- and dendro-architectonic changes of neurons in the limbic system in the mouse pilocarpine model of temporal lobe epilepsy. Epilepsy Res, 2010, 89(1): 43-51.
41. Bortel A, Levesque M, Biagini G, et al. Convulsive status epilepticus duration as determinant for epileptogenesis and interictal discharge generation in the rat limbic system. Neurobiol Dis, 2010, 40(2): 478-489.
42. Levesque M, Bortel A, Gotman J, et al. High-frequency (80-500 Hz) oscillations and epileptogenesis in temporal lobe epilepsy. Neurobiol Dis, 2011, 42(3): 231-241.
43. Kleen JK, Scott RC, Holmes GL, et al. Hippocampal interictal spikes disrupt cognition in rats. Ann Neurol, 2010, 67(2): 250-257.
44. Scorza FA, Arida RM, Naffah-Mazzacoratti Mda G, et al. The pilocarpine model of epilepsy: what have we learned?. An Acad Bras Cienc, 2009, 81(3): 345-365.
45. Arida RM, Scorza FA, Peres CA, et al. The course of untreated seizures in the pilocarpine model of epilepsy. Epilepsy Res, 1999, 34(2-3): 99-107.
46. Curia G, Longo D, Biagini G, et al. The pilocarpine model of temporal lobe epilepsy. J Neurosci Methods, 2008, 172(2): 143-157.
47. Priel MR, dos Santos NF, Cavalheiro EA. Developmental aspects of the pilocarpine model of epilepsy. Epilepsy Res, 1996, 26(1): 115-121.
48. Leite JP, Bortolotto ZA, Cavalheiro EA. Spontaneous recurrent seizures in rats: an experimental model of partial epilepsy. Neurosci Biobehav Rev, 1990, 14(4): 511-517.
49. Furtado Mde A, Braga GK, Oliveira JA, et al. Behavioral, morphologic, and electroencephalographic evaluation of seizures induced by intrahippocampal microinjection of pilocarpine. Epilepsia, 2002, 43 (Suppl 5): 37-39.
50. Pitkanen A, Sutula TP. Is epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurol, 2002, 1(3): 173-181.
51. Cavazos JE, Das I, Sutula TP. Neuronal loss induced in limbic pathways by kindling: evidence for induction of hippocampal sclerosis by repeated brief seizures. J Neurosci, 1994, 14(5 Pt 2): 3106-3121.
52. Gorter JA, van Vliet EA, Lopes da Silva FH. Which insights have we gained from the kindling and post-status epilepticus models? J Neurosci Methods, 2015, 4(1): S0165-0270.
53. Sharma AK, Reams RY, Jordan WH, et al. Mesial temporal lobe epilepsy: pathogenesis, induced rodent models and lesions. Toxicol Pathol, 2007,35(7): 984-999.

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