电刺激癫痫动物模型的研究进展_Journal of Epilepsy

Authors：

 苏磊 , 韩涛 , 臧轲君 , 位坤坤 , 王玉良 , 王胜军 , 赵秀鹤 , 迟兆富 ,  刘学伍

山东大学齐鲁医院神经内科, 济南, 250012;

Corresponding author：

刘学伍, Email: snlxw1966@163.com

Keywords：

电刺激; 电点燃; 动物模型; 自发性癫痫发作; 病理机制

DOI：

10.7507/2096-0247.2016

Video：

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癫痫以脑神经元异常放电引起反复痫性发作为特征。建立癫痫动物模型对研究癫痫的发病机制及治疗具有重要意义。近年来建立了多种动物模型, 主要包括化学点燃和电点燃模型等。经典的癫痫电点燃是对大脑边缘结构进行重复的电刺激, 导致逐渐增强的后放电和行为学上的癫痫发作。电点燃形成后, 即使不再给予刺激, 异常的痫性放电可以持续很长时间, 甚至终生。电刺激癫痫动物模型具有诱导致痫的优点, 而且与人类癫痫发生和形成极为相似。现就电点燃模型、电刺激的部位、参数, 动物点燃的行为表现、点燃方法及病理机制进行综述

Citation： 苏磊, 韩涛, 臧轲君, 位坤坤, 王玉良, 王胜军, 赵秀鹤, 迟兆富, 刘学伍. 电刺激癫痫动物模型的研究进展. Journal of Epilepsy, 2016, 2(1): 48-54. doi: 10.7507/2096-0247.2016 Copy

1.	Goddard GV. Development of epileptic seizures through brain stimulation at low intensity. Nature, 1967, 214 (19) :1020-1021.
2.	Shaw P. Molecular and cellular pathways of neurodegeneration in motor neurone disease. Neurol Neurosurg Psychiatry, 2005(76): 1046-1057.
3.	Lothman EW, Williamson JM.Rapid kindling with recurrent hippocampal seizures. Epil Res, 1993, 14 (3) :209-220.
4.	Mansoureh Eslami, Elham Ghanbari, Mohammad Sayyah, et al. Traumatic brain injury accelerates kindling epileptogenesis in rats. Neurological Research, 2015, Aug 27: 1743132815Y0000000086. [Epub ahead of print].
5.	Simonato M, Brooks-Kayal AR, Engel Jr, et al.The challenge and promise of anti-epileptic therapy development in animal models.Lancet Neurol, 2014, 13 (4):949-960.
6.	Polli RS, Malheiros JM, Santos R Dos, et al. Changes in hippocampal volume are correlated with cell loss but not with seizure frequency in two chronic models of temporal lobe epilepsy. Front Neurol, 2014, 5 (10): 111.
7.	Brandt C, Glien M, Potschka H, et al. Loscher.Epileptogenesis and neuropathology after different types of status epilepticus induced by prolonged electrical stimulation of the basolateral amygdala in rats. Epilepsy Res, 2003, 55 (3): 83-103.
8.	Pitkanen A, Nehlig A, Galanopoulou AS, et al. Issues related to development of antiepileptogenic therapies. Epilepsia, 2013, 54 (Suppl 4): 35-43.
9.	van Vliet EA, Edelbroek PM, Gorter JA. Improved seizure control by alternating therapy of levetiracetam and valproate in epileptic rats. Epilepsia, 2010, 51 (20): 362-370.
10.	Norwood BA, Bumanglag AV, Nicolato E, et al. Classic hippocampal sclerosis and hippocampal-onset epilepsy produced by a single cryptic episode of focal hippocampal excitation in awake rats. J Comp Neurol, 2010, 518 (21): 3381-3407.
11.	Ebert U, Rundfeldt C, Löscher W. Characterization of phenytoin-resistant kindled rats, a new model of drug-resistant partial epilepsy: influence of experimental and environmental factors. Epilepsy Research, 1999, 33(2-3): 199-215.
12.	Leung LS, Boon KA. Kindling in the posterior cingulate cortex: electrographic and behavioral characteristics. Electroencephalogr Clin Neurophysiol, 1990, 76(2): 177-186.
13.	Bertram E. Functional anatomy of spontaneous seizures in a rat model of limbic epilepsy. Epilepsia, 1997, 38(1): 95-105.
14.	Goddard GV, Mcintyre DC, Leech CK. A premanent chang in brain function resulting from daily electrical stimulation. Exp Neu rol, 1969, 25(12): 295-330.
15.	Racine RJ. Modification of seizure activity by electrical stimulation-Ⅱ, Motor seizurs. Electroencephalogy Clin Neuro physiol, 1972, 32(8): 281-294.
16.	Wada JA, Sato M. Generalized convulaive seizures induced by daily electrical stimulation of the amygdala in cats. Neurology, 1974, 15(8): 465-478.
17.	Morimoto K, Fahnestock M, Racine RJ. Kindling and status epilepticus models of epilepsy: rewiring the brain. Prog Neurobiol, 2004, 73 (2): 1-60.
18.	Lothman EW, Hat lelid JM, Zorums ki CF, et al. Inding with rapidly recurring hippocampal seizures. Brain Res, 1985, 360(20): 83-91.
19.	Mody I. Synaptic plasticity in kindling. Adv Neurol, 1999, 79(13): 631-643.
20.	Gortera Jan A, Fernando H, Lopes da Silva, et al. Which insights have we gained from the kindling and post-status epilepticus models? J Neumeth, 2015, 13(3): 25.
21.	Waldbaum S, Dudek FE. Single and repetitive paired-pulse suppression: a parametric analysis and assessment of usefulness in Epilepsy Res. Epilepsia, 2009, 50 (33): 904-916.
22.	Kamphuis W, Lopes da Silva FH, Wadman WJ. Changes in local evoked potentials in the rat hippocampus (CA1) during kindling epileptogenesis. Brain Res, 1988, 440 (1): 205-215.
23.	Zhao D, Leung LS. Hippocampal kindling induced paired-pulse depression in the dentate gyrus and paired-pulse facilitation in CA3. Brain Res, 1992, 58 (2): 163-167.
24.	Maru E, Goddard GV. Alteration in dentate neuronal activities associated with perforant path kindling. III. Enhancement of synaptic inhibition. Exp Neurol, 1987, 96 (18): 46-60.
25.	Goldberg EM, Coulter DA. Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction. Nature Rev Neurosci, 2013, 14 (21): 337-349.
26.	Gutierrez R, einemann U. Kindling induces transient fast inhibition in the dentate gyrus-CA3 projection. Eur J Neurosci, 2001, 13 (1): 1371-1379.
27.	罗强. NMDA受体与癫痫.国外医学儿科学分册, 2000, 27(6) :298-301.
28.	Köhr G. Kindling increases N-methyl-d-aspartate potency at single N-methyl-d-aspartate channels in dentate gyrus granule cells. Neuroscience, 1994, 62(4): 975-981.
29.	贺侃.即刻早期基因与癫痫.国外医学儿科分册, 2002, 29(1): 37-39.
30.	赵世刚, 罗强, 吴希如.遗传性癫痫易感大鼠P77PMC海马苔藓纤维发芽的研究.北京大学学报, 2001, 33(2): 101-104.
31.	戴永强, 胡学强.大鼠电点燃模型海马可塑性改变及其致病机制.中华神经医学杂志, 2005, 4(10) : 983-986.
32.	Zhu WJ, Roper SN. Brain-derived neurotrophic factor enhances fast excitatory synaptic transmission in human epileptic dentate gyrus. Ann Neurol, 2001, 50(2): 188-194.
33.	Shinoda H, Schwartz JP, Nadi NS. Amygdaloid kindling of rats increases preprosomatostatin mRNA and somatostatin without affecting glutamic acid decarboxylase (GAD) mRNA or GAD. Brain Res Mol Brain Res, 1989, 5 (19): 243-246.
34.	Potschka H, Krupp E, Lorch B, et al. Kindling-induced overexpression of Homer 1A and its functional implications for epileptogenesis. Eur J Neurosci, 2002, 16 (2): 2157-2165.
35.	Gu J, Lynch BA, Elashoff M, et al. The antiepileptic drug levetiracetam selectively modifies kindling-induced alterations in gene expression in the temporal lobe of rats. Eur J Neurosci, 2004, 19 (4): 334-345.
36.	Vezzani A, Michalkiewicz M, Richichi C, et al. Seizure susceptibility and epileptogenesis are decreased in transgenic rats overexpressing neuropeptide Y. Neuroscience, 2002, 110 (22): 237-243.
37.	刘庆祝, 王峰, 孙涛, 等.大鼠岛叶与杏仁核电点燃癫痫模型的相关性研究.宁夏医科大学学报, 2009, 31(6): 732-734.
38.	Sayin U, Osting S, Sutula T, et al. Spontaneous seizures and loss of axo-axonic and axo-somatic inhibition induced by repeated brief seizures in kindled rats. J Neurosci, 2003, 23 (7): 2759-2768.
39.	Brandt C, Ebert U, Loscher W. Epilepsy induced by extended amygdala-kindling in rats: lack of clear association between development of spontaneous seizures and neuronal damage. Epilepsy Res, 2004, 62 (4): 135-156.
40.	Grauert A, Engel D, Ruiz AJ. Endogenous zinc depresses GABAergic transmission via T-type Ca(2+) channels and broadens the time window for integration of glutamatergic inputs in dentate granule cells. J Physiol, 2014, 592 (112): 67-86.
41.	Rattka M, Brandt C, Loscher W. The intrahippocampal kainate model of temporal lobe epilepsy revisited: epileptogenesis, behavioral and cognitive alterations, pharmacological response, and hippoccampal damage in epileptic rats. Epilepsy Res, 2013, 103 (20):135-152.

1. Goddard GV. Development of epileptic seizures through brain stimulation at low intensity. Nature, 1967, 214 (19) :1020-1021.
2. Shaw P. Molecular and cellular pathways of neurodegeneration in motor neurone disease. Neurol Neurosurg Psychiatry, 2005(76): 1046-1057.
3. Lothman EW, Williamson JM.Rapid kindling with recurrent hippocampal seizures. Epil Res, 1993, 14 (3) :209-220.
4. Mansoureh Eslami, Elham Ghanbari, Mohammad Sayyah, et al. Traumatic brain injury accelerates kindling epileptogenesis in rats. Neurological Research, 2015, Aug 27: 1743132815Y0000000086. [Epub ahead of print].
5. Simonato M, Brooks-Kayal AR, Engel Jr, et al.The challenge and promise of anti-epileptic therapy development in animal models.Lancet Neurol, 2014, 13 (4):949-960.
6. Polli RS, Malheiros JM, Santos R Dos, et al. Changes in hippocampal volume are correlated with cell loss but not with seizure frequency in two chronic models of temporal lobe epilepsy. Front Neurol, 2014, 5 (10): 111.
7. Brandt C, Glien M, Potschka H, et al. Loscher.Epileptogenesis and neuropathology after different types of status epilepticus induced by prolonged electrical stimulation of the basolateral amygdala in rats. Epilepsy Res, 2003, 55 (3): 83-103.
8. Pitkanen A, Nehlig A, Galanopoulou AS, et al. Issues related to development of antiepileptogenic therapies. Epilepsia, 2013, 54 (Suppl 4): 35-43.
9. van Vliet EA, Edelbroek PM, Gorter JA. Improved seizure control by alternating therapy of levetiracetam and valproate in epileptic rats. Epilepsia, 2010, 51 (20): 362-370.
10. Norwood BA, Bumanglag AV, Nicolato E, et al. Classic hippocampal sclerosis and hippocampal-onset epilepsy produced by a single cryptic episode of focal hippocampal excitation in awake rats. J Comp Neurol, 2010, 518 (21): 3381-3407.
11. Ebert U, Rundfeldt C, Löscher W. Characterization of phenytoin-resistant kindled rats, a new model of drug-resistant partial epilepsy: influence of experimental and environmental factors. Epilepsy Research, 1999, 33(2-3): 199-215.
12. Leung LS, Boon KA. Kindling in the posterior cingulate cortex: electrographic and behavioral characteristics. Electroencephalogr Clin Neurophysiol, 1990, 76(2): 177-186.
13. Bertram E. Functional anatomy of spontaneous seizures in a rat model of limbic epilepsy. Epilepsia, 1997, 38(1): 95-105.
14. Goddard GV, Mcintyre DC, Leech CK. A premanent chang in brain function resulting from daily electrical stimulation. Exp Neu rol, 1969, 25(12): 295-330.
15. Racine RJ. Modification of seizure activity by electrical stimulation-Ⅱ, Motor seizurs. Electroencephalogy Clin Neuro physiol, 1972, 32(8): 281-294.
16. Wada JA, Sato M. Generalized convulaive seizures induced by daily electrical stimulation of the amygdala in cats. Neurology, 1974, 15(8): 465-478.
17. Morimoto K, Fahnestock M, Racine RJ. Kindling and status epilepticus models of epilepsy: rewiring the brain. Prog Neurobiol, 2004, 73 (2): 1-60.
18. Lothman EW, Hat lelid JM, Zorums ki CF, et al. Inding with rapidly recurring hippocampal seizures. Brain Res, 1985, 360(20): 83-91.
19. Mody I. Synaptic plasticity in kindling. Adv Neurol, 1999, 79(13): 631-643.
20. Gortera Jan A, Fernando H, Lopes da Silva, et al. Which insights have we gained from the kindling and post-status epilepticus models? J Neumeth, 2015, 13(3): 25.
21. Waldbaum S, Dudek FE. Single and repetitive paired-pulse suppression: a parametric analysis and assessment of usefulness in Epilepsy Res. Epilepsia, 2009, 50 (33): 904-916.
22. Kamphuis W, Lopes da Silva FH, Wadman WJ. Changes in local evoked potentials in the rat hippocampus (CA1) during kindling epileptogenesis. Brain Res, 1988, 440 (1): 205-215.
23. Zhao D, Leung LS. Hippocampal kindling induced paired-pulse depression in the dentate gyrus and paired-pulse facilitation in CA3. Brain Res, 1992, 58 (2): 163-167.
24. Maru E, Goddard GV. Alteration in dentate neuronal activities associated with perforant path kindling. III. Enhancement of synaptic inhibition. Exp Neurol, 1987, 96 (18): 46-60.
25. Goldberg EM, Coulter DA. Mechanisms of epileptogenesis: a convergence on neural circuit dysfunction. Nature Rev Neurosci, 2013, 14 (21): 337-349.
26. Gutierrez R, einemann U. Kindling induces transient fast inhibition in the dentate gyrus-CA3 projection. Eur J Neurosci, 2001, 13 (1): 1371-1379.
27. 罗强. NMDA受体与癫痫.国外医学儿科学分册, 2000, 27(6) :298-301.
28. Köhr G. Kindling increases N-methyl-d-aspartate potency at single N-methyl-d-aspartate channels in dentate gyrus granule cells. Neuroscience, 1994, 62(4): 975-981.
29. 贺侃.即刻早期基因与癫痫.国外医学儿科分册, 2002, 29(1): 37-39.
30. 赵世刚, 罗强, 吴希如.遗传性癫痫易感大鼠P77PMC海马苔藓纤维发芽的研究.北京大学学报, 2001, 33(2): 101-104.
31. 戴永强, 胡学强.大鼠电点燃模型海马可塑性改变及其致病机制.中华神经医学杂志, 2005, 4(10) : 983-986.
32. Zhu WJ, Roper SN. Brain-derived neurotrophic factor enhances fast excitatory synaptic transmission in human epileptic dentate gyrus. Ann Neurol, 2001, 50(2): 188-194.
33. Shinoda H, Schwartz JP, Nadi NS. Amygdaloid kindling of rats increases preprosomatostatin mRNA and somatostatin without affecting glutamic acid decarboxylase (GAD) mRNA or GAD. Brain Res Mol Brain Res, 1989, 5 (19): 243-246.
34. Potschka H, Krupp E, Lorch B, et al. Kindling-induced overexpression of Homer 1A and its functional implications for epileptogenesis. Eur J Neurosci, 2002, 16 (2): 2157-2165.
35. Gu J, Lynch BA, Elashoff M, et al. The antiepileptic drug levetiracetam selectively modifies kindling-induced alterations in gene expression in the temporal lobe of rats. Eur J Neurosci, 2004, 19 (4): 334-345.
36. Vezzani A, Michalkiewicz M, Richichi C, et al. Seizure susceptibility and epileptogenesis are decreased in transgenic rats overexpressing neuropeptide Y. Neuroscience, 2002, 110 (22): 237-243.
37. 刘庆祝, 王峰, 孙涛, 等.大鼠岛叶与杏仁核电点燃癫痫模型的相关性研究.宁夏医科大学学报, 2009, 31(6): 732-734.
38. Sayin U, Osting S, Sutula T, et al. Spontaneous seizures and loss of axo-axonic and axo-somatic inhibition induced by repeated brief seizures in kindled rats. J Neurosci, 2003, 23 (7): 2759-2768.
39. Brandt C, Ebert U, Loscher W. Epilepsy induced by extended amygdala-kindling in rats: lack of clear association between development of spontaneous seizures and neuronal damage. Epilepsy Res, 2004, 62 (4): 135-156.
40. Grauert A, Engel D, Ruiz AJ. Endogenous zinc depresses GABAergic transmission via T-type Ca(2+) channels and broadens the time window for integration of glutamatergic inputs in dentate granule cells. J Physiol, 2014, 592 (112): 67-86.
41. Rattka M, Brandt C, Loscher W. The intrahippocampal kainate model of temporal lobe epilepsy revisited: epileptogenesis, behavioral and cognitive alterations, pharmacological response, and hippoccampal damage in epileptic rats. Epilepsy Res, 2013, 103 (20):135-152.

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