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
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摘要
目的用两种方法建立颞叶耐药癫痫模型,探讨哪种方法更适合建立多药耐药颞叶癫痫模型。方法选用SD大鼠130只,10只作为正常组,120只分别制作杏仁核和匹罗卡品模型,模型成功后用抗癫痫药苯巴比妥和苯妥英钠或卡马西平进行筛选,分别选择10只杏仁核模型和匹罗卡品模型比较两种方法建立的模型癫痫发作持续时间、发作频率、发作级别、脑电图及电镜下超微结构的变化。结果成功制作杏仁核模型31只,匹罗卡品模型29只,匹罗卡品模型癫痫发作频率(2. 09±0. 044)高于杏仁核组(1. 01±0. 037),持续时间(61. 37±4. 22)长于杏仁核组(43. 16±5. 91),而癫痫发作的级别无明显差异;经过耐药性癫痫模型的筛选,选出杏仁核耐药模型8只,匹罗卡品耐药模型12只。匹罗卡品模型与杏仁核模型相比脑电频率更高,波幅增宽,超微结构的损伤更严重。结论匹罗卡品模型自发性率高,耐药率高,脑电变化明显,超微结构损伤重,更适合耐药性癫痫机制的研究。
Objective To establish a model of temporal lobe epilepsy by 2 methods,and to compare the characteristics of the amygdale EEG and seizure severity,the study investigated which one more suitable for a multi-drug resistant model of temporal lobe epilepsy. Methods A total of 130 rats,10 rats as normal group,120 rats were selected to prepare the model of epilepsy by chronic stimulation of amygaloid basal lateral nucleus or intraperitonial injection of pilocarpine. Pharmacoresistant epileptic rats were selected according their response to phenobabital and phenytoin or carbamazepine. Seizure severity,frequency,and duration,amydala EEG and the hippocampal ultrastrcture were compared between the two models.Results 31 rats were kindled successfully by amygale stimulation,the other 29 epileptic rats were prepared by intraperitonial injection of pilocarpine. We noted that the frequency of the spontaneous seizures in the pilocarpine-induced epileptic model( 2. 09 ± 0. 044) was higher than that of the amygdale kindled model( 1. 01 ± 0. 037),and the duration of epileptic seizures( 61. 37 ± 4. 22) was longer than that of the amygdale kindled model( 43. 16 ± 5. 91). Seizure severity displayed no difference between the two epileptic models. The damages of hippocampal ultrastructure in the pilocarpine-induced epileptic model was more serious than that of the amygdale kindled model. Conclusion The rate of the spontaneous epileptic seizures and the pharmacoresistance was higher in the pilocarpine-induced model of epilepsy than that of the amygdale kindling model. It was more suitable for investigating the mechanism of pharmacoresistant epilepsy.
Objective To establish a model of temporal lobe epilepsy by 2 methods,and to compare the characteristics of the amygdale EEG and seizure severity,the study investigated which one more suitable for a multi-drug resistant model of temporal lobe epilepsy. Methods A total of 130 rats,10 rats as normal group,120 rats were selected to prepare the model of epilepsy by chronic stimulation of amygaloid basal lateral nucleus or intraperitonial injection of pilocarpine. Pharmacoresistant epileptic rats were selected according their response to phenobabital and phenytoin or carbamazepine. Seizure severity,frequency,and duration,amydala EEG and the hippocampal ultrastrcture were compared between the two models.Results 31 rats were kindled successfully by amygale stimulation,the other 29 epileptic rats were prepared by intraperitonial injection of pilocarpine. We noted that the frequency of the spontaneous seizures in the pilocarpine-induced epileptic model( 2. 09 ± 0. 044) was higher than that of the amygdale kindled model( 1. 01 ± 0. 037),and the duration of epileptic seizures( 61. 37 ± 4. 22) was longer than that of the amygdale kindled model( 43. 16 ± 5. 91). Seizure severity displayed no difference between the two epileptic models. The damages of hippocampal ultrastructure in the pilocarpine-induced epileptic model was more serious than that of the amygdale kindled model. Conclusion The rate of the spontaneous epileptic seizures and the pharmacoresistance was higher in the pilocarpine-induced model of epilepsy than that of the amygdale kindling model. It was more suitable for investigating the mechanism of pharmacoresistant epilepsy.
引文
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[12]Volk HA,Arabadzisz D,Fritschy JM,et al.Antiepileptic drug-resistant rats differ from drug-responsive rats in hippocampal neurodegeneration and gaba(a)receptor ligand binding in a model of temporal lobe epilepsy[J].Neurobiology of Disease,2006,21:633-646.
[13]Bethmann K,Brandt C,Loscher W.Resistance to phenobarbital extends to phenytoin in a rat model of temporal lobe epilepsy[J].Epilepsia,2007,48:816-826.
[14]Wang Y,Zhou D,Wang B,et al.A kindling model of pharmacoresistant temporal lobe epilepsy in sprague-dawley rats induced by coriaria lactone and its possible mechanism[J].Epilepsia,2003,44:475-488.
[15]Gao J,Yao H,Pan XD,et al.Alteration of mitochondrial function and ultrastructure in the hippocampus of pilocarpine-treated rat[J].Epilepsy Research,2014,108:162-170.
[2]Sebe JY,Baraban SC.The promise of an interneuron-based cell therapy for epilepsy[J].Developmental Neurobiology,2011,71:107-117.
[3]Ding D,Hong Z,Wang WZ,et al.Assessing the disease burden due to epilepsy by disability adjusted life year in rural china[J].Epilepsia,2006,47:2032-2037.
[4]Chen N,Zhang H,Gao XD,et al.Neuroprotective effects of vagus nerve stimulation on hippocampal neurons in intractable epilepsy[J].Medical Hypotheses,2013,81:1066-1068.
[5]Buckmaster PS,Haney MM.Factors affecting outcomes of pilocarpine treatment in a mouse model of temporal lobe epilepsy[J].Epilepsy Research,2012,102:153-159.
[6]Wang L,Shi J,Wu G,et al.Hippocampal low-frequency stimulation increased sv2a expression and inhibited the seizure degree in pharmacoresistant amygdala-kindling epileptic rats[J].Epilepsy Research,2014,108:1483-1491.
[7]Shi J,Zhou F,Wang LK,et al.Synaptic vesicle protein2a decreases in amygdaloid-kindling pharmcoresistant epileptic rats.Journal of Huazhong University of Science and Technology[J].Medical Sciences,2015,35:716-722.
[8]Scorza FA,Arida RM,Naffah-Mazzacoratti Mda G,et al.The pilocarpine model of epilepsy:What have we learned[J].Anais da Academia Brasileira de Ciencias,2009,81:345-365.
[9]Monaghan MM,Menegola M,Vacher H,et al.Altered expression and localization of hippocampal a-type potassium channel subunits in the pilocarpine-induced model of temporal lobe epilepsy[J].Neuroscience,2008,156:550-562.
[10]Curia G,Longo D,Biagini G,et al.The pilocarpine model of temporal lobe epilepsy[J].Journal of Neuroscience Methods,2008,172:143-157.
[11]Volk HA,Loscher W.Multidrug resistance in epilepsy:Rats with drug-resistant seizures exhibit enhanced brain expression of p-glycoprotein compared with rats with drug-responsive seizures[J].Brain,2005,128:1358-1368.
[12]Volk HA,Arabadzisz D,Fritschy JM,et al.Antiepileptic drug-resistant rats differ from drug-responsive rats in hippocampal neurodegeneration and gaba(a)receptor ligand binding in a model of temporal lobe epilepsy[J].Neurobiology of Disease,2006,21:633-646.
[13]Bethmann K,Brandt C,Loscher W.Resistance to phenobarbital extends to phenytoin in a rat model of temporal lobe epilepsy[J].Epilepsia,2007,48:816-826.
[14]Wang Y,Zhou D,Wang B,et al.A kindling model of pharmacoresistant temporal lobe epilepsy in sprague-dawley rats induced by coriaria lactone and its possible mechanism[J].Epilepsia,2003,44:475-488.
[15]Gao J,Yao H,Pan XD,et al.Alteration of mitochondrial function and ultrastructure in the hippocampus of pilocarpine-treated rat[J].Epilepsy Research,2014,108:162-170.