难治性癫痫动物模型的研究进展_Journal of Epilepsy

Authors：

陈睿 ¹ ,  薛国芳 ²

1. ;
2. ;

Corresponding author：

薛国芳, Email: xueguofangty@163.com

Keywords：

难治性癫痫; 匹罗卡品; 海人酸; 杏仁核; 6 Hz 角膜点燃

DOI：

10.7507/2096-0247.20210071

Video：

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难治性癫痫患者占癫痫患者总人数的 20%～30%。然而，难治性癫痫的形成机制尚未完全清楚，且对患者及其家属造成较大危害和负担。由于难治性癫痫患者脑组织标本难以获取，因此目前仍需通过模型研究其机制。难治性癫痫动物模型能模拟人类难治性癫痫的病理改变、脑电图特点、行为学特点等，有助于探索其发病机制及治疗手段。本综述概述了难治性癫痫动物模型中的化学点燃模型、电点燃模型和遗传性动物模型，以期为今后选择合适的模型提供帮助。

Citation： 陈睿, 薛国芳. 难治性癫痫动物模型的研究进展. Journal of Epilepsy, 2021, 7(5): 431-435. doi: 10.7507/2096-0247.20210071 Copy

1.	Kwan P, Arzimanoglou A, Berg A, et al. Definition of drug resistant epilepsy: consensus proposal by the Ad Hoc Task Force of the ILAE Commission on Therapeutic Strategies. Akt Neurol, 2010, 37(8): 1069-1077.
2.	Janson Marnie T, Bainbridge Jacquelyn L, et al. Continuing burden of refractory epilepsy. The Annals of pharmacotherapy, 2021, 55(3): 406-408.
3.	Yoo JY, Panov F. Identification and treatment of drug-resistant epilepsy. CONTINUUM: Lifelong Learning in Neurology, 2019, 25(2): 362-380.
4.	张英菊, 侯丽亚, 冯丽荣, 等. 难治性癫痫的抗癫痫药物耐药性机制研究进展. 神经疾病与精神卫生, 2019, 19(6): 631-635.
5.	Löscher W. Animal models of intractable epilepsy. Progress in Neurobiology, 1997, 53(2): 239-258.
6.	Vizuete Adriana Fernanda K, Mittmann HM, Alberto GC, et al. Phase-dependent astroglial alterations in li-pilocarpine-induced status epilepticus in young rats. Neurochemical research, 2017, 42(10): 2730-2742.
7.	Marques-Carneiro J E, Persike D S, Litzahn J J, et al. Hippocampal proteome of rats subjected to the li-pilocarpine epilepsy model and the effect of carisbamate treatment. Pharmaceuticals, 2017, 10(3): 67.
8.	龙莉莉, 肖波, 李国良, 等. 氯化锂-匹罗卡品致大鼠的模型研究. 神经损伤与功能重建, 2010, 5(02): 83-88.
9.	Ji-Eun K, Kyung-Ok C. The pilocarpine model of temporal lobe epilepsy and EEG monitoring using radiotelemetry system in mice. Journal of visualized experiments: JoVE, 2018, (132): 56831.
10.	王丽琨, 周鑫, 伍国锋, 等. 建立杏仁核电刺激慢点燃和匹罗卡品化学点燃耐药性颞叶癫痫模型并对比癫痫发作和海马超微结构的变化. 中风与神经疾病杂志, 2019, 36(2): 112-115.
11.	陈姝璇, 王丽琨, 伍国锋. 杏仁核电点燃癫(痫)模型与氯化锂-匹罗卡品大鼠癫(痫)模型的对比研究. 癫癎与神经电生理学杂志, 2016, 25(3): 129-132.
12.	顾友余, 陈文杰, 秦炯. 癫痫研究中常用的体外模型及啮齿类动物模型. 生理科学进展, 2019, 50(05): 375-380.
13.	Lévesque M, Avoli M. The kainic acid model of temporal lobe epilepsy. Neuroscience and Biobehavioral Reviews, 2013, 37(10): 2887-99.
14.	朱飞, 郎森阳, 王群. 颞叶癫痫动物模型. 中国抗癫痫协会. 第六届 CAAE 国际癫痫论坛摘要集. 中国抗癫痫协会: 中国抗癫痫协会, 2015: 90-91.
15.	王军, 李承宗, 龙浩, 等. 颞叶癫痫动物模型研究进展. 中国神经精神疾病杂志, 2019, 45(1): 60-64.
16.	Giorgia C, Alberto P, Mariana A, et al. High concordance between hippocampal transcriptome of the mouse intra-amygdala kainic acid model and human temporal lobe epilepsy. Epilepsia, 2020, 61(12): 2795-2810.
17.	王玉娇, 陈烨, 师忠芳, 等. 大鼠海人酸点燃海马与杏仁核颞叶癫痫模型发作特点及海马病理学改变的研究. 中华神经外科杂志, 2019, (3): 305-311.
18.	Zachary Z, Mikaela B, Caara L, et al. Targeting the mouse ventral hippocampus in the intrahippocampal kainic acid model of temporal lobe epilepsy. eNeuro, 2018, 5(4): 0158-18.
19.	Sehirli Umit S, Ozlem K, Kutluhan T, et al. Differences in neurodegeneration between kainic acid-injected GAERS and wistar rats. Turkish neurosurgery, 2019, 29(4): 478-485.
20.	周鑫, 陈中玮, 王丽琨, 等. 大鼠杏仁核快速电刺激点燃癫痫模型的建立. 中华医学会神经病学分会第十次全国脑电图与癫痫诊治进展高级讲授班及学术研讨会, 2015: 1.
21.	马新财, 孙蒙蒙, 呼奶英, 等. 大鼠海马和杏仁核电点燃癫痫模型的比较. 山西医科大学学报, 2017, 48(10): 986-991.
22.	Yuanxin H, Lin W, Siying R, et al. The Expression of ZnT3 and GFAP is potentiated in the hippocampus of drug-resistant epileptic rats induced by amygdala kindling. Neuroimmunomodulation, 2020, 27(2): 104-112.
23.	Nirwan N, Vyas P, Vohora D. Animal models of status epilepticus and temporal lobe epilepsy: a narrative review. Reviews in the Neurosciences, 2018, 29(7): 757-770.
24.	高青, 曾贵荣, 欧阳冬生. 6 Hz 角膜点燃癫痫动物模型的研究进展. 中国实验动物学报, 2019, 27(03): 393-398.
25.	Zhu L, Rekha J, Evelyne G, et al. Deletion of semaphorin 3F in interneurons is associated with decreased GABAergic neurons, autism-like behavior, and increased oxidative stress cascades. Molecular neurobiology, 2019, 56(8): 5520-5538.
26.	Wolfgang L, Heidrun P, M S S, et al. Drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options. Pharmacological reviews, 2020, 72(3): 606-638.
27.	Patel DC, Tewari BP, Chaunsali L, et al. Neuron–glia interactions in the pathophysiology of epilepsy. Nature Reviews Neuroscience, 2019, 20(5): 282-297.
28.	Steinhäuser C, Grunnet M, Carmignoto G. Crucial role of astrocytes in temporal lobe epilepsy. Neuroscience, 2016, 323: 157-69.
29.	Clark I A, Vissel B. Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents. Journal of Neuroinflammation, 2016, 13(1): 236.
30.	李巷, 潘建青, 康慧聪, 等. p-JNK/p-c-Jun 通路参与大鼠杏仁核点燃癫痫模型. 神经损伤与功能重建, 2016, 11(6): 473-475.
31.	Carme A, de Lemos Luisa, Ester V, et al. Role of JNK isoforms in the kainic acid experimental model of epilepsy and neurodegeneration. Frontiers in bioscience (Landmark edition), 2017, 22: 795-814.
32.	Feng Z X, Yuan L, Maraj A M, et al. Microglial mTOR is neuronal protective and anti-epileptogenic in the pilocarpine model of temporal lobe epilepsy. The Journal of neuroscience: the official journal of the Society for Neuroscience, 2020, 40(40): 7593-7608.

1. Kwan P, Arzimanoglou A, Berg A, et al. Definition of drug resistant epilepsy: consensus proposal by the Ad Hoc Task Force of the ILAE Commission on Therapeutic Strategies. Akt Neurol, 2010, 37(8): 1069-1077.
2. Janson Marnie T, Bainbridge Jacquelyn L, et al. Continuing burden of refractory epilepsy. The Annals of pharmacotherapy, 2021, 55(3): 406-408.
3. Yoo JY, Panov F. Identification and treatment of drug-resistant epilepsy. CONTINUUM: Lifelong Learning in Neurology, 2019, 25(2): 362-380.
4. 张英菊, 侯丽亚, 冯丽荣, 等. 难治性癫痫的抗癫痫药物耐药性机制研究进展. 神经疾病与精神卫生, 2019, 19(6): 631-635.
5. Löscher W. Animal models of intractable epilepsy. Progress in Neurobiology, 1997, 53(2): 239-258.
6. Vizuete Adriana Fernanda K, Mittmann HM, Alberto GC, et al. Phase-dependent astroglial alterations in li-pilocarpine-induced status epilepticus in young rats. Neurochemical research, 2017, 42(10): 2730-2742.
7. Marques-Carneiro J E, Persike D S, Litzahn J J, et al. Hippocampal proteome of rats subjected to the li-pilocarpine epilepsy model and the effect of carisbamate treatment. Pharmaceuticals, 2017, 10(3): 67.
8. 龙莉莉, 肖波, 李国良, 等. 氯化锂-匹罗卡品致大鼠的模型研究. 神经损伤与功能重建, 2010, 5(02): 83-88.
9. Ji-Eun K, Kyung-Ok C. The pilocarpine model of temporal lobe epilepsy and EEG monitoring using radiotelemetry system in mice. Journal of visualized experiments: JoVE, 2018, (132): 56831.
10. 王丽琨, 周鑫, 伍国锋, 等. 建立杏仁核电刺激慢点燃和匹罗卡品化学点燃耐药性颞叶癫痫模型并对比癫痫发作和海马超微结构的变化. 中风与神经疾病杂志, 2019, 36(2): 112-115.
11. 陈姝璇, 王丽琨, 伍国锋. 杏仁核电点燃癫(痫)模型与氯化锂-匹罗卡品大鼠癫(痫)模型的对比研究. 癫癎与神经电生理学杂志, 2016, 25(3): 129-132.
12. 顾友余, 陈文杰, 秦炯. 癫痫研究中常用的体外模型及啮齿类动物模型. 生理科学进展, 2019, 50(05): 375-380.
13. Lévesque M, Avoli M. The kainic acid model of temporal lobe epilepsy. Neuroscience and Biobehavioral Reviews, 2013, 37(10): 2887-99.
14. 朱飞, 郎森阳, 王群. 颞叶癫痫动物模型. 中国抗癫痫协会. 第六届 CAAE 国际癫痫论坛摘要集. 中国抗癫痫协会: 中国抗癫痫协会, 2015: 90-91.
15. 王军, 李承宗, 龙浩, 等. 颞叶癫痫动物模型研究进展. 中国神经精神疾病杂志, 2019, 45(1): 60-64.
16. Giorgia C, Alberto P, Mariana A, et al. High concordance between hippocampal transcriptome of the mouse intra-amygdala kainic acid model and human temporal lobe epilepsy. Epilepsia, 2020, 61(12): 2795-2810.
17. 王玉娇, 陈烨, 师忠芳, 等. 大鼠海人酸点燃海马与杏仁核颞叶癫痫模型发作特点及海马病理学改变的研究. 中华神经外科杂志, 2019, (3): 305-311.
18. Zachary Z, Mikaela B, Caara L, et al. Targeting the mouse ventral hippocampus in the intrahippocampal kainic acid model of temporal lobe epilepsy. eNeuro, 2018, 5(4): 0158-18.
19. Sehirli Umit S, Ozlem K, Kutluhan T, et al. Differences in neurodegeneration between kainic acid-injected GAERS and wistar rats. Turkish neurosurgery, 2019, 29(4): 478-485.
20. 周鑫, 陈中玮, 王丽琨, 等. 大鼠杏仁核快速电刺激点燃癫痫模型的建立. 中华医学会神经病学分会第十次全国脑电图与癫痫诊治进展高级讲授班及学术研讨会, 2015: 1.
21. 马新财, 孙蒙蒙, 呼奶英, 等. 大鼠海马和杏仁核电点燃癫痫模型的比较. 山西医科大学学报, 2017, 48(10): 986-991.
22. Yuanxin H, Lin W, Siying R, et al. The Expression of ZnT3 and GFAP is potentiated in the hippocampus of drug-resistant epileptic rats induced by amygdala kindling. Neuroimmunomodulation, 2020, 27(2): 104-112.
23. Nirwan N, Vyas P, Vohora D. Animal models of status epilepticus and temporal lobe epilepsy: a narrative review. Reviews in the Neurosciences, 2018, 29(7): 757-770.
24. 高青, 曾贵荣, 欧阳冬生. 6 Hz 角膜点燃癫痫动物模型的研究进展. 中国实验动物学报, 2019, 27(03): 393-398.
25. Zhu L, Rekha J, Evelyne G, et al. Deletion of semaphorin 3F in interneurons is associated with decreased GABAergic neurons, autism-like behavior, and increased oxidative stress cascades. Molecular neurobiology, 2019, 56(8): 5520-5538.
26. Wolfgang L, Heidrun P, M S S, et al. Drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options. Pharmacological reviews, 2020, 72(3): 606-638.
27. Patel DC, Tewari BP, Chaunsali L, et al. Neuron–glia interactions in the pathophysiology of epilepsy. Nature Reviews Neuroscience, 2019, 20(5): 282-297.
28. Steinhäuser C, Grunnet M, Carmignoto G. Crucial role of astrocytes in temporal lobe epilepsy. Neuroscience, 2016, 323: 157-69.
29. Clark I A, Vissel B. Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents. Journal of Neuroinflammation, 2016, 13(1): 236.
30. 李巷, 潘建青, 康慧聪, 等. p-JNK/p-c-Jun 通路参与大鼠杏仁核点燃癫痫模型. 神经损伤与功能重建, 2016, 11(6): 473-475.
31. Carme A, de Lemos Luisa, Ester V, et al. Role of JNK isoforms in the kainic acid experimental model of epilepsy and neurodegeneration. Frontiers in bioscience (Landmark edition), 2017, 22: 795-814.
32. Feng Z X, Yuan L, Maraj A M, et al. Microglial mTOR is neuronal protective and anti-epileptogenic in the pilocarpine model of temporal lobe epilepsy. The Journal of neuroscience: the official journal of the Society for Neuroscience, 2020, 40(40): 7593-7608.

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难治性癫痫动物模型的研究进展

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