颞叶癫痫发生与海马可塑性改变的相关性研究
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摘要
目的：观察海马可塑性改变对颞叶癫痫发生的影响，探讨二者之间的相关性。
方法：本研究分三部分：①通过向Sprague-Dawley大鼠腹腔注射氯化锂-匹罗卡品制作慢性颞叶癫痫动物模型。观察其致痫后的行为学改变，并比较其改变。采用光学显微镜、电子显微镜对大鼠海马及齿状回组织中细胞损伤和苔藓纤维出芽的形态学特征进行观察、描述并定量评价，用t检验进行统计学分析。②采用免疫组织化学技术检测N-cadherin在大鼠海马及齿状回中致痫组和对照组中的表达，统计N-cadherin的表达情况，采用t检验、Bivariate相关分析来探讨其与可塑性改变的关系。③观察大鼠脑电的变化，并在颞叶癫痫模型大鼠离体海马脑片上记录自发性癫痫样电活动，应用t检验、Bivariate相关分析及Partial相关分析从多方面来了解海马可塑性改变与颞叶癫痫发生的相关性。
结果：氯化锂-匹罗卡品诱发的大鼠癫痫模型发作过程包括急性期、潜伏期、慢性期3个相对独立的时期，可以观察到自发性痫性发作，是理想的颞叶癫痫模型，适用于探讨颞叶癫痫的发生机制；致痫SD大鼠可以观察到海马神经元损伤、苔藓纤维出芽等可塑性改变，且随时间进行性增加；N-cadherin的表达明显增加，表达的时间和位置均与海马可塑性改变相一致，N-cadherin的表达与神经元损伤呈负相关；SE大鼠离体海马脑片CA3区可记录到自发性癫痫样电活动；神经元损伤与自发性癫痫样放电呈负相关，但在控制N-cadherin的表达后无相关性；N-cadherin的表达与自发性癫痫样放电呈正相关。
结论：氯化锂-匹罗卡品致痫具有与人类颞叶癫痫相似的特征，是理想的颞叶癫痫模型，适用于探讨颞叶癫痫的发生机制。SD大鼠致痫后可以观察到一系列神经系统可塑性改变；N-cadherin的表达与神经元损伤呈负相关，可能参与海马可塑性改变的过程；慢性颞叶癫痫大鼠离体海马脑片经刺激后可有自发性癫痫样电活动；海马神经元损伤与N-cadherin的表达呈负相关，通过可塑性改变对自发性癫痫样放电产生影响，但二者之间无直接的相关性；N-cadherin的表达与自发性癫痫样放电有明显的正相关。
Objective: To investigate the effects of the hippocampal plasticity on epileptogenesis of the temporal lobe epilepsy and to study the correlation between them.
Methods: Our research includes three parts: (l)In this study, adult Sprague-Dawley rat chronical seizure model was firstly established following status epilepticus induced by lithium-pilocarpine, this model is similar to the major character of human temporal lobe epilepsy. Afterwards we investigate the spontaneous seizures every day, record and analyse. We use the opticmicroscope and electronmicroscope to observe the morphologic character of hippocampal plasticity such as neuronal death and mossy fiber sprount dynamicly and quantitative analysis it by t-test. (2)With the immunohistochemistry method ,We detect the expression of the N-cadherin in experimental group and compare group and t-test, bivariate correlate evaluation were made in order to find the relationship between hippocampal plasticity and expression of the N-cadherin. (3)Record the electroencephalogram of the SD rat dynamically.We use extracellular microelectrode to recorde the epileptiform burst in the CA3 area of the hippocampus in TLE rat slices. We use t-test, bivariate correlate evaluation and partial correlate evaluation to analyse the relationship between hippocampal plasticity and epileptogenesis of the temporal lobe epilepsy.
Results: Lithium-pilocarpine induced SD rat model includes acute period, latent period and chronic period. Spontaneous recurrent seizures can be observed during the chronic period.we can study the epileptogenesis of the temporal lobe epilepsy through this rat model because the clinical characters of this one is similar with that of the human being. The morphologic character of hippocampal plasticity such as neuronal death and mossy fiber sprount and synapse reformation emerged step by step. Expression of the N-cadherin in experimental group increased gradully accord to the time. The expression of the N-cadherin is correlated with the neuronal death negatively. Spontaneous epileptiform burst in the CA3 area of the hippocampus in TLE rat slices were recorded. The neuronal death is correlated with the epileptiform burst negatively.But the correlation between neuronal death and epileptiform burst dimissed when we avioded the influence of the the expression of the N-cadherin. The expression of the N-cadherin is correlated with the epileptiform burst.
Conclusion: Lithium-pilocarpine induced SD rat model can be used to study the epileptogenesis of the temporal lobe epilepsy because the clinical characters of this one is similar with that of the human being.Neural plastic change can be oberserved during the chronic period in the rat model. The expression of the N-cadherin is correlated with the neuronal death negatively and may participate the change of the Neural plastic. Spontaneous epileptiform burst in the CA3 area of the hippocampus in TLE rat slices can be recorded. The neuronal death is correlated with the expression of the N-cadherin negatively and its influence on epileptiform burst were given through plasticity change,that is tosay there is no correlation between them. The expression of the N-cadherin is correlated with the epileptiform burst.
方法：本研究分三部分：①通过向Sprague-Dawley大鼠腹腔注射氯化锂-匹罗卡品制作慢性颞叶癫痫动物模型。观察其致痫后的行为学改变，并比较其改变。采用光学显微镜、电子显微镜对大鼠海马及齿状回组织中细胞损伤和苔藓纤维出芽的形态学特征进行观察、描述并定量评价，用t检验进行统计学分析。②采用免疫组织化学技术检测N-cadherin在大鼠海马及齿状回中致痫组和对照组中的表达，统计N-cadherin的表达情况，采用t检验、Bivariate相关分析来探讨其与可塑性改变的关系。③观察大鼠脑电的变化，并在颞叶癫痫模型大鼠离体海马脑片上记录自发性癫痫样电活动，应用t检验、Bivariate相关分析及Partial相关分析从多方面来了解海马可塑性改变与颞叶癫痫发生的相关性。
结果：氯化锂-匹罗卡品诱发的大鼠癫痫模型发作过程包括急性期、潜伏期、慢性期3个相对独立的时期，可以观察到自发性痫性发作，是理想的颞叶癫痫模型，适用于探讨颞叶癫痫的发生机制；致痫SD大鼠可以观察到海马神经元损伤、苔藓纤维出芽等可塑性改变，且随时间进行性增加；N-cadherin的表达明显增加，表达的时间和位置均与海马可塑性改变相一致，N-cadherin的表达与神经元损伤呈负相关；SE大鼠离体海马脑片CA3区可记录到自发性癫痫样电活动；神经元损伤与自发性癫痫样放电呈负相关，但在控制N-cadherin的表达后无相关性；N-cadherin的表达与自发性癫痫样放电呈正相关。
结论：氯化锂-匹罗卡品致痫具有与人类颞叶癫痫相似的特征，是理想的颞叶癫痫模型，适用于探讨颞叶癫痫的发生机制。SD大鼠致痫后可以观察到一系列神经系统可塑性改变；N-cadherin的表达与神经元损伤呈负相关，可能参与海马可塑性改变的过程；慢性颞叶癫痫大鼠离体海马脑片经刺激后可有自发性癫痫样电活动；海马神经元损伤与N-cadherin的表达呈负相关，通过可塑性改变对自发性癫痫样放电产生影响，但二者之间无直接的相关性；N-cadherin的表达与自发性癫痫样放电有明显的正相关。
Objective: To investigate the effects of the hippocampal plasticity on epileptogenesis of the temporal lobe epilepsy and to study the correlation between them.
Methods: Our research includes three parts: (l)In this study, adult Sprague-Dawley rat chronical seizure model was firstly established following status epilepticus induced by lithium-pilocarpine, this model is similar to the major character of human temporal lobe epilepsy. Afterwards we investigate the spontaneous seizures every day, record and analyse. We use the opticmicroscope and electronmicroscope to observe the morphologic character of hippocampal plasticity such as neuronal death and mossy fiber sprount dynamicly and quantitative analysis it by t-test. (2)With the immunohistochemistry method ,We detect the expression of the N-cadherin in experimental group and compare group and t-test, bivariate correlate evaluation were made in order to find the relationship between hippocampal plasticity and expression of the N-cadherin. (3)Record the electroencephalogram of the SD rat dynamically.We use extracellular microelectrode to recorde the epileptiform burst in the CA3 area of the hippocampus in TLE rat slices. We use t-test, bivariate correlate evaluation and partial correlate evaluation to analyse the relationship between hippocampal plasticity and epileptogenesis of the temporal lobe epilepsy.
Results: Lithium-pilocarpine induced SD rat model includes acute period, latent period and chronic period. Spontaneous recurrent seizures can be observed during the chronic period.we can study the epileptogenesis of the temporal lobe epilepsy through this rat model because the clinical characters of this one is similar with that of the human being. The morphologic character of hippocampal plasticity such as neuronal death and mossy fiber sprount and synapse reformation emerged step by step. Expression of the N-cadherin in experimental group increased gradully accord to the time. The expression of the N-cadherin is correlated with the neuronal death negatively. Spontaneous epileptiform burst in the CA3 area of the hippocampus in TLE rat slices were recorded. The neuronal death is correlated with the epileptiform burst negatively.But the correlation between neuronal death and epileptiform burst dimissed when we avioded the influence of the the expression of the N-cadherin. The expression of the N-cadherin is correlated with the epileptiform burst.
Conclusion: Lithium-pilocarpine induced SD rat model can be used to study the epileptogenesis of the temporal lobe epilepsy because the clinical characters of this one is similar with that of the human being.Neural plastic change can be oberserved during the chronic period in the rat model. The expression of the N-cadherin is correlated with the neuronal death negatively and may participate the change of the Neural plastic. Spontaneous epileptiform burst in the CA3 area of the hippocampus in TLE rat slices can be recorded. The neuronal death is correlated with the expression of the N-cadherin negatively and its influence on epileptiform burst were given through plasticity change,that is tosay there is no correlation between them. The expression of the N-cadherin is correlated with the epileptiform burst.
引文
1. Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalography and Clinical Neurophysiology 1972b; 32: 281-294.
2. Stables JP,Bertram EH,White HS,Coulter DA,Dichter MA,Jacobs MP,Loscher W,Lowenstein DH,Moshe SL,Noebels JL and Davis M.Models forepilepsy and epileptogenesis:report from the NIH workshop,Bethesda,Maryland.Epilepsia 2002;43:1410-1420.
3. Borges K,Gearing M,McDermott GD,et al. Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model.Experimental Neurology, 2003,182(1):21-34.
4. Elger CE. Epilepsy:A model for the study of brain function. Lancet Neural, 2005, 4(1):3-5.
5. Epilepsy Foundation of America Working Group on Status Epilepticus. Treatment of convulsive status epilepticus. JAMA 1993;270: 854-859.
6. Sperk G. Kainic acid seizures in the rat. Progr Neurobiol, 1994,42: 1-32.
7. Lothman EW,Bertram EH. Epileptogenic effects of status epileptica. Epilepsia, 1993, 34 Suppl: S59-70.
8. Mohdin R, Robert E, Sompong S, et al. Evidence that injury-induced changes in hippocampal neuronal calcium dynamics during epileptogenesis cause acquired epilepsy. Proceedings of the National Academy of Science of the USA(PNAS), 2004, 101:17522-17527.
9. Coulter DA. Chronic epileptogeoic cellular alterations in the limbic system after status epilepticus. Epilepsia, 1999, 40(suppl 1):S23-33.
10. Turski WA. Cavalheiro EA. Schwarz M. et al. Limbic seizures produced by pilocarpine in rats: behavioral, electroencephalographic and neuropathological study. Behavioral Brain Research, 1983,9:315-335.
11. 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, 1991,32:778-782.
12. Marinho MM, Sousa FC, Bruin VM, Vale MR, Viana GS. Effects of lithium, alone or associated with pilocarpine, on muscarinic and dopaminergic receptors and on phosphoinositide metabolism in rat hippocampus and striatum. Neurochem. Int, 1998, 33: 299-306.
13. Savolainen KM, Hirvonen MR. Second messengers in cholinergic induced convulsions and neuronal injury. Toxicol Lett, 1992, 64: 437-445.
14. Einet H, Kofman O, Itkin O, et al. Augmentation of lithium's behavioral effect by inositol uptake inhibitors. J Neural Transrn, 1998,105:31-38.
15. Clifford DB, Olney LW, Maniotis A, et al. The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures. Neuroscience, 1987,23:953-968.
16. Clifford DB, Olney LW, Maniotis A, et al. The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures. Neuroscience, 1987,23:953-968.
17. Ormandy GC, Jope RS, Snead OC. Anticonvulsant actions of MK-801 in the lithium-pilocarpine model of status epilepticus in rats. Exp Neurol, 1989,106:172-180.
18. Coulter DA. Chronic epileptogeoic cellular alterations in the limbic system after status epilepticus. Epilepsia, 1999,40(suppl 1):S23-33.
19. Engel JJR. Introdution to temporal lobe epilepsy. Epilepsy research, 1996, 26:141-150.
20. Seidenberg M, Kelly KG, Parrish J et al. Ipsilateral and contralateral MRI volumetric abnormalities in chronic unilateral temporal lobe epilepsy and their clinical correlates. Epilepsia, 2005, 46(3):420-30.
21. Janszky J, Janszky I, Schulz R et al. Temporal lobe epilepsy with hippocampal sclerosis:predictors for long-term surgical outcome. Brain, 2005,128 (Pt2):395-404.
22. Sogawa Y, Monokoshi M, Silveira DC, Cha BH, Cilio MR, McCabe BK, Liu X, Hu Y, Holmes GL. Timing of cognitive deficits following neonatal seizures: relationship to histological changes in the hippocampus. Brain Res Dev Brain Res, 2001,131:73-83.
23. Peredery O, Persinger MA, Parker G, Mastrosov L. Temperal changes in neuronal drooprt following inductions of lithium-pilocarpine seizures in the rat. Brain Res, 2000, 881: 9-17.
24. BouilleretV, Ridoux V, Depaulis A, et al. Recurrent seizures and hippocampal sclerosis . following intrahippocampal kainite injection in adult mice: electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy. Neuroscience, 1999,89:717-729.
25. Ben Ari Y. Limbic seizure and brain damage produced by kainic acid:mechanisms and relevance to human temporal lobe epilepsy. J Neuroscience. 1985,14(2):375-403.
26. Henshall DC, Sinclair JS, Simon RP. Relationship between seizure-induced transcription of the DNA damage-inducible gene GADD45, DNA fragmentation and neuronal death in focally evoked bmbic epilepsy. J Neurochem, 1999,73(4): 1573-1583.
27. Priel MR, Ferreiea-Santos N, Cavalheiro EA. Developmental aspects of the pilocarpme model of epilepsy. Epilepsy Research, 1996, 26: 115-121.
28. Choi DW.excitotoxic cell death. Neurobiol,1992,23:1261～1276.
29. Van der Hel WS, Notenboom RG, Bos IW et al. Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy. Neurology, 2005, 64(2) :326-333.
30. Mikati M. Neuronal cell death in a rat model of mesial temporal lobe epilepsy is induced by the initial status epilepticus and not by later repeated spontaneous seizures. Epilepsia, 2004,45(3): 296-297.
31. Andre V, ferrandon A, Marescaux C, et al. The lesion and epileptogenic consequences of lithium-pilocarpine-induced status epilepticus are affected by previous exposure to isolated seizures: effects of amygdale kindling and maximal electroshocks. Neuroscience, 2000, 99:469-481.
32. Shetty AK, Turner DA. Fetal hippocampal cells grafted to kainate lesioned CA3 region of adult hippocampus suppress aberrant, supragran-ular sprouting of host mossy fibers. Exp Neurol, 1997,143 (2): 231-245.
33. Anderson P, Bliss VP, Skrede KK. Lamellar organization of hippocampal excitatory pathways. Exp Brain Res, 1971,13:222-238.
34. Perez-Clausell J, Danscher G: Release of zine sulphide accumulation into synaptic clefts fiber in vivo injection of sodium sulphide. Brain Res 1986,358-362.
35. Howell GA: Stimulation induced uptake and release of zinc in hippocampal slices. Nature 1984,308:736.
36. Danscher G, Zimmer J: An improved timm sulphid silver method for light and electron microscopic localization of heavy metals in biological tissue. Histochem;1978,55:27.
37. Shibley H, Smith BN. Pilocarpine-induced status epilepticus result in mossy fiber sprouting and spontaneous seizures in C57BL/6 and CD-1 mice. Epilepsy RES, 2002, 49(2): 109-120.
38. Sloviter RS. Status epilepticus-induced neuronal injury and network reorganization.Epilepsia, 1999,40:S34-39.
39. Conner-Ken TA, Simmons DR, Peterson GM, et al. Evidence for the corelease of dynorphin and glutamate from rat hippocampal mossy fiber terminals. J.Neurochem, 1993, 61:627-636.
40. Wuarin JP, Dudek EE. Electrographic seizures and new recurrent excitatory circuits in the dentate gyrus of hippocampal slices from kainite-treated epileptic rats. J, Neurosci, 1996,16(14): 4438-4448.
41. Cavazos JE, Zhang, P, Qazi R, Sutula TP. Ultrastructural features of sprouted mossy fiber synapses in kindled and kainic acid-treated rats. J Comp Neurol, 2003,458:272-292.
42. Wuarin JP, Dudek FE. Excitatory synaptic input to granule cells increases with time after kainate treatment. J Neurophysiol, 2001, 85:1067-1077.
43. Nissinen J, Lukasiuk K, Pitkanen A. Is mossy fiber sprouting present at the time of the first spontaneous seizures in rat experimental temporal lobe epilepsy? Hippocampus, 2001,11:299-310.
44. Raol YS, Budreck EC, Brooks-Kayal AR. Epilepsy after early-life seizures can be independent of hippocampal injury. Ann Neurol, 2003, 53:503-511.
1. Katz LC, Shatz CJ. Synaptic activity and the construction of cortical circuits. Science,1996,274:1123-1133.
2. Sogawa Y, Monokoshi M, Silveira DC, Cha BH, Cilio MR, McCabe BK, Liu X, Hu Y, Holmes GL. Timing of cognitive deficits following neonatal seizures: relationship to histological changes in the hippocampus. Brain Res Dev Brain Res, 2001,131:73-83.
3. Peredery O, Persinger MA, Parker G, Mastrosov L. Temperal changes in neuronal drooprt following inductions of lithium-pilocarpine seizures in the rat. Brain Res, 2000, 881:9-17.
4. Kotloski R, Lynch M, Lauersdorf S, Sutula T. Recurrent brief seizures induce progressive hippocampal neuron loss and memory deficits. Prog Brain Res, 2002,135:95-110.
5. Grattan-Smith P, Hopkins I, Shield L, Boldt D. Status epilepticus induced brain damage and opercular syndrome in childhood. Dev Med Child Neurol, 2000, 42:428-429.
6. Smith SJ. Neuronal cytomechanics: the actin-based motility of growth cone. Science, 1988,242:708-711.
7. Racine RJ. Modification of seizure activity by electrical stimulation: II Motor seizures. Electrorencephalogr. Clin Neurophysiol, 1972, 32: 281-294.
8. Friedman HV, Bresler T, Garner CC, Ziv NE. Assembly of new individuall excitatory synapses;time course and temporal order of synaptic molecule recruitment. Neuron, 2000,27:57-69.
9. Tang L, Hung CP, Schuman EM. A role for the cadherin familiy of cell adhesion molecules in hippocampal long-term potentiation.Neuron,1998, 20:1165-1175.
10. Bozdagi O, Shan W , Tanaka H, Benson DL, Huntley GW. Increasing numbers of synaptic puncta during late-phase LTP: N-cadherin is synthesized,recruited to synaptic sites,and required for potentation. Neuron ,2000,28:245-259.
11. Tanaka H, Shan W, Phillips GR, Arndt K, Bozdagi O, Shapiro L, Huntley GW, Benson DL, Colman DR. Molecular modification of N-cadherin in response to synaptic activity. Neuron 2000,25:93-107.
12. Togashi H, Abe K, Mizoguchi A, Takaoka K, Chisaka O, Takeichi M. Cadherin regulates dendritic spine morphogenesis. Neuron, 2002, 35:77-89.
13. Parent JM, Yu TW, Leibowitz DH, Geschwind DH, Sloviter RS, Lowenstein DH. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus.J Neurosci, 1997,17;3727-3738.
14. Parent JM, Tada E, Fike JR, Leibowitz DH. Inhibition of dentate grandule cell neurogenesis with brain irradiation dose not prvent seizure induced mossy fiber synaptic reorganization in the rat. J Neurosci, 1999, 19; 4508-4519.
15. Bendotti C, Pende M, Samanin R. Expression of GAP-43 in the gransule cells of rats hippocampus after seizure-induced sprouting of mossy fiber in situ hybridization and chemical studies.Eur J Neurosci,1994,6;509-515.
16. Redies C. Cadherins and the formation of neural circuity in the vertebrate CNS.Cell Tissue Res,1997,290;405-413.
17. Brose N. Synaptic cell adhesion proteins and synaptogenesis in the mammalian central nerous system. Naturwissenschaften, 1999, 86; 516-524.
18. Tepass U, Truong K, Godt D, Ikura M, Peifer M. Cadherin in embryonic and neural morphogenesis.Nat Rev Mol Cell Boil,2000,1;91-100.
19. Lee CH, Herman T, Clandinin TR, Zipursky SL. N-cadherin regulates target specificity in the Drosophila visual system. Neuron, 2001, 30:437-450.
20. Treubert-Zimmermann U, Heyers D, Redies C. Targeting axons to specific fiber tracts in vivo by altering cadherin expression. J Neurosci, 2002,22:7617-7626.
21. Masai I, Lele Z, Yamaguchi M, Komori A, Nakata A, Nishiwaki Y, Wada H, Tanaka H, Nojima Y, Hammerschmidt M, Wilson SW, Okamoto H. N-cadherin mediates retinal lamination, maintenance of forebrain compartments and patterning of retinal neuritis. Development, 2003,130:2479-2494.
1 韩济生主编。神经科学原理(下册)。北京：北京医科大学出版社，第2版。1993：1088-1089。
2 鞠躬主编。神经生物学。北京：人民卫生出版社，第1版。2004：608-621。
3 Prince DA. Physiological mechanisms of focal epileptogenesis. Epile psia 1985;26(suppl1):S3.
4 Dudley S, Dinnera, Silvia Nemea, Dileep Nair et al. EEG and evok ed potential recording from the subthalamic nucleus for deep brain stimulation of intractable epilepsy. Clinical Neurophysiology 113(2002);1391-1402.
5 McCormick DA, Contreras D. On the cellular and network bases of epileptic seizures. Annu Rev Physiol, 2001,63:815～846.
6 Johnston D, Amaral DG. Hippocampus. In Shepherd, GM (eds), Syn aptic organization of the brain. Oxford, New York, 1998: 417-458.
7 Gjerstad L, Andersen P, Langmoen IA, Lundervold A, Hablitz J. Sy naptic triggering of epileptiform discharges in Ca~(2+) pyramidal cells in vitro. Acta Physiol Scand 1981;113:245-252.
8 Behr J,Gloveli T, Gutierrez R,Heinemann U.Spread of low Mg~(2+) indu ced epileptiform activity from the rat entorhinal cortex to the hippo campus after kindling studied in vitro.Neurosci Lett 1996;216:41-44.
9 Andersen P, Soleng AF, Raastad M. The hippocampal lamella hypot hesis revisited. Brain Research, 2000, 886:165-171.
10 Anderson P, Bliss VP, Skrede KK. Lamellar organization of hippoca mpal excitatory pathways. Exp Brain Res, 1971,13:222-238.
11 吕国蔚主编。实验神经生物学。北京：科学出版社，第1版。2002：137-163。
12 Pumain R. Electrophysiological abnormalities in chronic epileptogeni c foci:an intracellular study.Brain Res 1981;219:445-450.
13 Andersen P, Bliss TP, Richards CD. Unit anlysis of hippocampal po pulation spikes. Exp Brain Res 1971;13:208-221.
14 Shuai J, Bikson M, Hahn PJ, Lian J, Durand DM. Ionic mechanis ms underlying spontaneous CA1 neuronal firing in Ca~(2+)-free solutio n. Biophys J 2003; 84: 2099-2111.
15 Staff NP, Jung H, Thiagarajan T, et al. Resting and active propertie s of pyramidal neurons in subiculum and CA1 of rat hippocampus. J Neurophysiol, 2000,84:2398-2408.
16 Bear J, Fountain NB, Lothman EW. Responses of the superficial en torhinal cortex in slices from naive and chronically epileptic rats. J neurophysiol, 1996,76(5):2928.
17 Rafiqu A, Zhang YF, Delorenzo RJ et al. Long-sustained epileptifor m activity in the hippocampal-parahippocampal slices:a model of sta tus epilepticus. J Neurophysiol,1995,74(5):2028-2029.
18 Klishin A, Tsintsadze T, Lozovaya N, Krishtal O. Latent N-methyl-D-aspartate receptors in the recurrent excitatory pathway between hi ppocampal CA1 pyramidal neurons: Ca~(2+)-dependent activation by bl oking A_1 adonosine receptors. Proc Natl Acad Sci 1995; 92: 12431-12435.
19 Bazan NG, Tu B, Rodriguez DT, Elena B. What synaptic lipid sign aling tells us about seizure-induced damage and epileptogenesis. Pro g Brain Res 2002; 135: 175-185.
20 Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr 2000; 130: 1007S-1015S.
21 Mathern GW, Babb TL, Armstrong DL. Hippocampal sclerosis. In:E ngel J, Pedley TA,eds. Epilepsy: a comprehensive textbook. Philadel phia: Lippincott-Raven Publishers, 1997:137-149.
22 Lothman EW, Bertram EH. Epileptogenic effects of status epileptica. Epilepsia,1993, 34 Suppl: S59-70.
23 Mikati M. Neuronal cell death in a rat model of mesial temporal lo be epilepsy is induced by the initial status epilepticus and not by later repeated spontaneous seizures. Epilepsia, 2004, 45(3): 296-297.
24 Shetty AK, Turner DA. Fetal hippocampal cells grafted to kainate lesioned CA3 region of adult hippocampus suppress aberrant.supragra nular sprouting of host mossy fibers.Exp Neurol, 1997, 143 (2):231-245.
1. Wiebe S, Blume WT, Girvin JP et al. A randomiomized, controlled trial of surgery for temporal lobe epilepsy. N Engt J Med,2001 , 345(5):311-318.
2. Schwartzkroin PA. In Epilepsy: models, mechanisms, and concepts. Edited by Schwartzkroin PA. 1993, London, Cambridge University Press, pp: 1-18.
3. Stables JP, Bertram EH, White HS, Coulter DA, Dichter MA, Jacobs MP, Loscher W, Lowenstein DH, Moshe SL, Noebels JL and Davis M. Models for epilepsy and epileptogenesis: report from the NIH workshop, Bethesda, Maryland. Epilepsia 2002; 43:1410-1420.
4. Borges K, Gearing M, McDermott GD et al. Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model.Experimental Neurology, 2003,182(1):21-34.
5. Elger CE. Epilepsy:A model for the study of brain function. Lancet Neural, 2005, 4(1):3-5.
6. Epilepsy Foundation of America Working Group on Status Epilepticus. Treatment of convulsive status epilepticus. JAMA 1993;270: 854-859.
7. Sperk G Kainic acid seizures in the rat. Progr Neurobiol, 1994,42: 1-32.
8. Lothman EW, Bertram EH. Epileptogenic effects of status epileptica. Epilepsia, 1993, 34 Suppl: S59-70.
9. Mohdin R, Robert E, Sompong S, et al. Evidence that injury-induced changes in hippocampal neuronal calcium dynamics during epileptogenesis cause acquired epilepsy. Proceedings of the National Academy of Science of the USA(PNAS), 2004, 101:17522-17527.
10. Coulter DA. Chronic epileptogeoic cellular alterations in the limbic system after status epilepticus. Epilepsia, 1999, 40(suppl 1):S23-33.
11. Goddard GV. The development of epileptic seizures through brain . stimulation at low intensity. Nature 1967; 214:1020-1021.
12. McIntyre DC, Poulter MO, Gilby K. Kindling: some old and some new. Epilepsy Res 2002; 50: 79-92.
13. Goddard GV, Mclntyre DC, Leech CK. A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol 1969; 25: 295-330.
14. Bradford HF, Peterson DW. Current views of the pathobiochemistry of epilepsy. Mol Aspects Med 1987; 9: 19-172.
15. Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalography and Clinical Neurophysiology 1972b; 32: 281-294.
16. Vreugdenhil M, Wadman WJ. Potassium currents in isolated CA1 neurons of the rat after kindling epileptogenesis Neuroscience 1995; 66: 805-813.
17. Racine RJ. Modification of seizure activity by electrical stimulation. I. After-discharge threshold. Electroencephalography and Clinical Neurophysiology 1972a; 32: 269-279.
18. Markram H, Sakmann B. Calcium transients in dendrites of neocortical neurons evoked by single subthreshold excitatory postsynaptic potentials via low-voltage-activated calcium channels. Proc natl Acad Sci USA 1994; 91:5207-5211.
19. Lisman E Goldring MA. Feasibility of long-term storage of graded information by the Ca~(2+)/calmodulin-dependent protein kinase molecules of the postsynaptic density. Proc natl Acatl Sci USA 1988; 85:5320-5324.
20. Miyakawa H, Ross WN, Jaffe DB, Callaway JC, Lasser-Ross N, Lisman JE, Johnston D. Synaptically activated increases in Ca~(2+) concentration in hippocampal CA1 pyramidal cells are primarily due to voltage-gated Ca~(2+) channels. Neuron 1992; 9: 1163-1173.
21. Regehr WG, Tank DW. Calcium concentration dynamics produced by synaptic activation of CAl hippocampal pyramidal cells. J Neurosci 1992;12:4202-4223.
22. Takahashi K, Wakamori M, Akai N. Hippocampal CAl pyramidal cells of rats have four voltage-dependent calcium conductances. Neurosci Lett 1989; 104: 229-234.
23. Carbone E, Lux HD. Kinetics of a low-voltage-activated calcium current in chick and rat sensory neurones. J Physiol 1987; 386: 547-570.
24. Jefferys GR. Basic mechanisms of focal epilepsy. Expl Physiol 1990; 75: 127-162.
25. Dawson RJ, Wallace DR. Kainic acid induced seizures in aged rats: neurochemical correlates. Brain Res Bull, 1992,29:45-566.
26. Holtmaat AJ, Goiter JA, De Wit J et al. Transient down regulation of Sema3A mRNA in a rat model for temporal lobe epilepsy. a novel molecular event potentially contributing to mossy fiber sprouting. Exp Neurol, 2003,182:142-150.
27. Sawamura A, Hashizume K, Yoshida K and Tanaka T. Kainic acid-induced substantia nigra seizure in rats: behavior, EEG and metabolism. Brain Research 2001 ;911:89-95.
28. Gorter JA, Goncalves PM, Vliet EA, et al. Neuronal cell death in a rat model for temporal lobe epilepsy is induced by the initial status epilepticus and not by later repcated spontaneous seizures. Epilepsia, 2003,44:647-658.
29. Leite JP, Bortolotto ZA, Cavalheiro EA. Spontaneous recurrent seizures in rats: an experimental model of partial epilepsy. Neurosci Biobehav Rev 1990; 14: 511-517.
30. Westbrook GL. Glutamate receptor update. Curr Opin Neurobiol 1994; 4: 337-346.
31. Coan EJ, Saywood W, Collingridge GL. MK-801 blocks NMDA receptor mediated synaptic transmission and long term potentiation in rat hippocampal slices. Neurosci Lett 1987; 80:111-114.
32. Collingridge GL, Kehl SJ, McLennan H. Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. J Physiol (London) 1983;334: 33-46.
33. Bliss TBP, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus (review). Nature 1993;361:31-39.
34. Tromner BL, Pasternak JF. NMDA receptor antagonists inhibit kindling epileptogenesis and seizure expression in developing rats. Dev Brain Res 1990; 53: 248-252.
35. Gilbert. Potentiation of inhibition with perforant path kindling: an NMDA-receptor dependent process. Brain Res 1991;564:109-116.
36. Yeh GC, Bonhaus DW, Nadler JV, McNamara JO. N-methyl-D-aspartate receptor plasticity in kindling: quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex. Proc Natl Acad Sci USA 1989; 86: 8157-8160.
37. McNamara JO, Russell RD, Rigsbee L, Bonhaus DW. Anti-convulsant and antiepileptogenic actions of MK-801 in kindling and electroshock models. Neuropharmacology 1988; 27:563-568.
38. Mody I, Heinemann U. NMDA receptors of dentate gyrus granule cells participate in synaptic transmission following kindling. Nature 1987; 326: 701-704.
39. Sutula T, Koch J, Golarai G, Watanabe Y, McNamara JO. NMDA receptor dependence of kindling and mossy fiber sprouting: evidence that the NMDA receptor regulates patterning of hippocampal circuits in the adult brain. J Neurosci 1996; 16:7398-7406.
40. Panchision DM, Gerwin CM, DeLorenzo RJ, Jakoi ER. Glutamate receptor activation regulates mRNA at both transcriptional and posttranscriptional levels. J Neurochem 1995:65: 969-977.
41. Perlin JB, Gerwin CM, Panchision DM, Vick RS, Jakoi ER, DeLorenzo RJ. Kindling produces long-lasting and selective changes in gene expression of hippocampal neurons. Proc Natl Acad Sci USA 1993; 90: 1741-1745.
42. Cavalheiro EA, Leite JP, Bortolotto ZA, Turski WA, lkonomidou C, Turski L. Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia 1991;32:778-782.
43. Mikati MA, Werner S, Gatt A, Liu Z, Rahmeh AA, Rachid RA, Stafstrom CE, Holmes GL. Consequences of a-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid receptor blockade during status epilepticus in the developing brain. Brain Res Dev Brain Res 1999; 113: 139-142.
44. Baran H, Loscher W, Mevissen M. The glycine/NMDA receptor partial agonist D-cycloserine blocks kainate-induced seizures in rats. Comparison with MK-801 and diazepam. Brain Res 1994; 652: 195-200.
45. MacGregor DG, Graham DI, Stone TW. The attenuation of kainate-induced neurotoxicity by chlormethiazole and its enhancement by dizocilpine, muscimol, and adenosine receptor agonists. Exp Neurol 1997; 148: 110-123.
46. Marinho MM, Sousa FC, Bruin VM, Vale MR, Viana GS. Effects of lithium, alone or associated with pilocarpine, on muscarinic and dopaminergic receptors and on phosphoinositide metabolism in rat hippocampus and striatum. Neurochem. Int, 1998, 33: 299-306.
47. Savolainen KM, Hirvonen MR. Second messengers in cholinergic-induced convulsions and neuronal injury. Toxicol Lett, 1992, 64: 437-445.
48. Einet H, Kofman O, Itkin O, et al. Augmentation of lithium's behavioral effect by inositol uptake inhibitors. J Neural Transrn, 1998,105:31-38.
49. Clifford DB, Olney LW, Maniotis A, et al. The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures. Neuroscience, 1987,23:953-968.
50. Clifford DB, Olney LW, Maniotis A, et al. The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures. Neuroscience, 1987,23:953-968.
51. Ormandy GC, Jope RS, Snead OC. Anticonvulsant actions of MK-801 in the lithium-pilocarpine model of status epilepticus in rats. Exp Neurol, 1989,106:172-180.
52. Coulter DA. Chronic epileptogeoic cellular alterations in the limbic system after status epilepticus. Epilepsia, 1999,40(suppl 1):S23-33.
1．张守信，金连弘。主编。神经生物学。北京：科学出版社，第1版。2002：537-591。
2. Levitan IB, Kaczmarek LK. The Neuron:Cell and Molecular Biology. 2nd ed. New York: Oxford University Press. 1997:373-467.
3. Sanes JR, Lichtman JW. Development of the vertebrate neuromuscular junction. Annu Rev Neurosci, 1999,22:389-442.
4. Smith SJ. Neuronal cytomechanics: the actin-based motility of growth cone. Science, 1988, 242:708-711.
5. Levitan IB, Kaczmarek LK. The Neuron:Cell and Molecular Biology. 2nd ed. New York: Oxford University Press. 1997:373-467.
6. N Uchida, Y Honjo, KR Johnson, MJ Wheelock and M Takeichi. The catenin/cadherin adhesion system is localized-in synaptic junctions bordering transmitter release zones. J cell Biol,1996;135(3):767-779.
7. Jun-ichiro Tsutsui, Maiko Moriyama, Naomichi Arima, Hindeo Ohtsubo, Hiromitsu Tanaka, and Massyuki Ozawa. Expression of Cadherin-Catenin Complexes in Human Leukemia Cell Lines. J. Biochem. (Tokyo), November 1996; 120:1034 - 1039.
8. Marie PJ, Debiais F, Hay E. Renulation of human cranial osteoblast phenotype by FGF-2, FGFR-2 and BMP-2 signalinng. J. Histol Histopathol, 2002, 17(3):877-885.
9. Tanaka H, Shan W, Phillips GR, Amdt K, Bozdagi O, Shapiro L, Huntley GW, Benson DL, Colman DR. Molecular modification of N-cadherin in response to synaptic activity. Neuron 2000, 25:93-107.
10. Togashi H, Abe K, Mizoguchi A, Takaoka K, Chisaka O, Takeichi M. Cadherin regulates dendritic spine morphogenesis. Neuron, 2002, 35:77-89.
11. Lee CH, Herman T, Clandinin TR, Zipursky SL. N-cadherin regulates target specificity in the Drosophila visual system. Neuron, 2001, 30:437-450.
12. Treubert-Zimmermann U, Heyers D, Redies C. Targeting axons to specific fiber tracts in vivo by altering cadherin expression. J Neurosci, 2002,22:7617-7626.
13. Masai I, Lele Z, Yamaguchi M, Komori A, Nakata A, Nishiwaki Y, Wada H, Tanaka H, Nojima Y, Hammerschmidt M, Wilson SW, Okamoto H. N-cadherin mediates retinal lamination, maintenance of forebrain compartments and patterning of retinal neuritis. Development, 2003,130:2479-2494.
14. Orsulic S, Huber O, Aberle H, et al. E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation. J Cell Sci, 1999,112:1237-1245.
15. Daniel JM, Reynolds AB. The catenin p120(ctn) interacts with kaiso, a novel BTB/POZ domain zinc finger transcription factor. Mol Cell Biol, 1999,19:3614-3623.
16. Imamura Y, Itoh M, Maeno Y, et al. Functional domains of alpha-catenin required for the strong state of cadhein based cell adhesion. J Cell Biol, 1999,144:1311-1322.
17. Hegland DD, Sullivan DM, Rovira H, et al. Regulation of endothelial cell adherens junctions by a ras dependent singal transduction pathway. Biochem Biophys Res commun,1999,260:371-376.
18. Ozawa M, Kemler R. Altered cell adhesion activity by pervanadate due to the dissociation of alpha-catenin from the E-cadherin-catenin complex. J Biol Chem, 1998,273:6166-6170.
19. Le TL, Yap AS, Stow JL. Recycling of E-caherin:a potential mechanism for regulating cadherin dynamics. J Cell Biol,1999,13:362-378.
2. Stables JP,Bertram EH,White HS,Coulter DA,Dichter MA,Jacobs MP,Loscher W,Lowenstein DH,Moshe SL,Noebels JL and Davis M.Models forepilepsy and epileptogenesis:report from the NIH workshop,Bethesda,Maryland.Epilepsia 2002;43:1410-1420.
3. Borges K,Gearing M,McDermott GD,et al. Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model.Experimental Neurology, 2003,182(1):21-34.
4. Elger CE. Epilepsy:A model for the study of brain function. Lancet Neural, 2005, 4(1):3-5.
5. Epilepsy Foundation of America Working Group on Status Epilepticus. Treatment of convulsive status epilepticus. JAMA 1993;270: 854-859.
6. Sperk G. Kainic acid seizures in the rat. Progr Neurobiol, 1994,42: 1-32.
7. Lothman EW,Bertram EH. Epileptogenic effects of status epileptica. Epilepsia, 1993, 34 Suppl: S59-70.
8. Mohdin R, Robert E, Sompong S, et al. Evidence that injury-induced changes in hippocampal neuronal calcium dynamics during epileptogenesis cause acquired epilepsy. Proceedings of the National Academy of Science of the USA(PNAS), 2004, 101:17522-17527.
9. Coulter DA. Chronic epileptogeoic cellular alterations in the limbic system after status epilepticus. Epilepsia, 1999, 40(suppl 1):S23-33.
10. Turski WA. Cavalheiro EA. Schwarz M. et al. Limbic seizures produced by pilocarpine in rats: behavioral, electroencephalographic and neuropathological study. Behavioral Brain Research, 1983,9:315-335.
11. 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, 1991,32:778-782.
12. Marinho MM, Sousa FC, Bruin VM, Vale MR, Viana GS. Effects of lithium, alone or associated with pilocarpine, on muscarinic and dopaminergic receptors and on phosphoinositide metabolism in rat hippocampus and striatum. Neurochem. Int, 1998, 33: 299-306.
13. Savolainen KM, Hirvonen MR. Second messengers in cholinergic induced convulsions and neuronal injury. Toxicol Lett, 1992, 64: 437-445.
14. Einet H, Kofman O, Itkin O, et al. Augmentation of lithium's behavioral effect by inositol uptake inhibitors. J Neural Transrn, 1998,105:31-38.
15. Clifford DB, Olney LW, Maniotis A, et al. The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures. Neuroscience, 1987,23:953-968.
16. Clifford DB, Olney LW, Maniotis A, et al. The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures. Neuroscience, 1987,23:953-968.
17. Ormandy GC, Jope RS, Snead OC. Anticonvulsant actions of MK-801 in the lithium-pilocarpine model of status epilepticus in rats. Exp Neurol, 1989,106:172-180.
18. Coulter DA. Chronic epileptogeoic cellular alterations in the limbic system after status epilepticus. Epilepsia, 1999,40(suppl 1):S23-33.
19. Engel JJR. Introdution to temporal lobe epilepsy. Epilepsy research, 1996, 26:141-150.
20. Seidenberg M, Kelly KG, Parrish J et al. Ipsilateral and contralateral MRI volumetric abnormalities in chronic unilateral temporal lobe epilepsy and their clinical correlates. Epilepsia, 2005, 46(3):420-30.
21. Janszky J, Janszky I, Schulz R et al. Temporal lobe epilepsy with hippocampal sclerosis:predictors for long-term surgical outcome. Brain, 2005,128 (Pt2):395-404.
22. Sogawa Y, Monokoshi M, Silveira DC, Cha BH, Cilio MR, McCabe BK, Liu X, Hu Y, Holmes GL. Timing of cognitive deficits following neonatal seizures: relationship to histological changes in the hippocampus. Brain Res Dev Brain Res, 2001,131:73-83.
23. Peredery O, Persinger MA, Parker G, Mastrosov L. Temperal changes in neuronal drooprt following inductions of lithium-pilocarpine seizures in the rat. Brain Res, 2000, 881: 9-17.
24. BouilleretV, Ridoux V, Depaulis A, et al. Recurrent seizures and hippocampal sclerosis . following intrahippocampal kainite injection in adult mice: electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy. Neuroscience, 1999,89:717-729.
25. Ben Ari Y. Limbic seizure and brain damage produced by kainic acid:mechanisms and relevance to human temporal lobe epilepsy. J Neuroscience. 1985,14(2):375-403.
26. Henshall DC, Sinclair JS, Simon RP. Relationship between seizure-induced transcription of the DNA damage-inducible gene GADD45, DNA fragmentation and neuronal death in focally evoked bmbic epilepsy. J Neurochem, 1999,73(4): 1573-1583.
27. Priel MR, Ferreiea-Santos N, Cavalheiro EA. Developmental aspects of the pilocarpme model of epilepsy. Epilepsy Research, 1996, 26: 115-121.
28. Choi DW.excitotoxic cell death. Neurobiol,1992,23:1261～1276.
29. Van der Hel WS, Notenboom RG, Bos IW et al. Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy. Neurology, 2005, 64(2) :326-333.
30. Mikati M. Neuronal cell death in a rat model of mesial temporal lobe epilepsy is induced by the initial status epilepticus and not by later repeated spontaneous seizures. Epilepsia, 2004,45(3): 296-297.
31. Andre V, ferrandon A, Marescaux C, et al. The lesion and epileptogenic consequences of lithium-pilocarpine-induced status epilepticus are affected by previous exposure to isolated seizures: effects of amygdale kindling and maximal electroshocks. Neuroscience, 2000, 99:469-481.
32. Shetty AK, Turner DA. Fetal hippocampal cells grafted to kainate lesioned CA3 region of adult hippocampus suppress aberrant, supragran-ular sprouting of host mossy fibers. Exp Neurol, 1997,143 (2): 231-245.
33. Anderson P, Bliss VP, Skrede KK. Lamellar organization of hippocampal excitatory pathways. Exp Brain Res, 1971,13:222-238.
34. Perez-Clausell J, Danscher G: Release of zine sulphide accumulation into synaptic clefts fiber in vivo injection of sodium sulphide. Brain Res 1986,358-362.
35. Howell GA: Stimulation induced uptake and release of zinc in hippocampal slices. Nature 1984,308:736.
36. Danscher G, Zimmer J: An improved timm sulphid silver method for light and electron microscopic localization of heavy metals in biological tissue. Histochem;1978,55:27.
37. Shibley H, Smith BN. Pilocarpine-induced status epilepticus result in mossy fiber sprouting and spontaneous seizures in C57BL/6 and CD-1 mice. Epilepsy RES, 2002, 49(2): 109-120.
38. Sloviter RS. Status epilepticus-induced neuronal injury and network reorganization.Epilepsia, 1999,40:S34-39.
39. Conner-Ken TA, Simmons DR, Peterson GM, et al. Evidence for the corelease of dynorphin and glutamate from rat hippocampal mossy fiber terminals. J.Neurochem, 1993, 61:627-636.
40. Wuarin JP, Dudek EE. Electrographic seizures and new recurrent excitatory circuits in the dentate gyrus of hippocampal slices from kainite-treated epileptic rats. J, Neurosci, 1996,16(14): 4438-4448.
41. Cavazos JE, Zhang, P, Qazi R, Sutula TP. Ultrastructural features of sprouted mossy fiber synapses in kindled and kainic acid-treated rats. J Comp Neurol, 2003,458:272-292.
42. Wuarin JP, Dudek FE. Excitatory synaptic input to granule cells increases with time after kainate treatment. J Neurophysiol, 2001, 85:1067-1077.
43. Nissinen J, Lukasiuk K, Pitkanen A. Is mossy fiber sprouting present at the time of the first spontaneous seizures in rat experimental temporal lobe epilepsy? Hippocampus, 2001,11:299-310.
44. Raol YS, Budreck EC, Brooks-Kayal AR. Epilepsy after early-life seizures can be independent of hippocampal injury. Ann Neurol, 2003, 53:503-511.
1. Katz LC, Shatz CJ. Synaptic activity and the construction of cortical circuits. Science,1996,274:1123-1133.
2. Sogawa Y, Monokoshi M, Silveira DC, Cha BH, Cilio MR, McCabe BK, Liu X, Hu Y, Holmes GL. Timing of cognitive deficits following neonatal seizures: relationship to histological changes in the hippocampus. Brain Res Dev Brain Res, 2001,131:73-83.
3. Peredery O, Persinger MA, Parker G, Mastrosov L. Temperal changes in neuronal drooprt following inductions of lithium-pilocarpine seizures in the rat. Brain Res, 2000, 881:9-17.
4. Kotloski R, Lynch M, Lauersdorf S, Sutula T. Recurrent brief seizures induce progressive hippocampal neuron loss and memory deficits. Prog Brain Res, 2002,135:95-110.
5. Grattan-Smith P, Hopkins I, Shield L, Boldt D. Status epilepticus induced brain damage and opercular syndrome in childhood. Dev Med Child Neurol, 2000, 42:428-429.
6. Smith SJ. Neuronal cytomechanics: the actin-based motility of growth cone. Science, 1988,242:708-711.
7. Racine RJ. Modification of seizure activity by electrical stimulation: II Motor seizures. Electrorencephalogr. Clin Neurophysiol, 1972, 32: 281-294.
8. Friedman HV, Bresler T, Garner CC, Ziv NE. Assembly of new individuall excitatory synapses;time course and temporal order of synaptic molecule recruitment. Neuron, 2000,27:57-69.
9. Tang L, Hung CP, Schuman EM. A role for the cadherin familiy of cell adhesion molecules in hippocampal long-term potentiation.Neuron,1998, 20:1165-1175.
10. Bozdagi O, Shan W , Tanaka H, Benson DL, Huntley GW. Increasing numbers of synaptic puncta during late-phase LTP: N-cadherin is synthesized,recruited to synaptic sites,and required for potentation. Neuron ,2000,28:245-259.
11. Tanaka H, Shan W, Phillips GR, Arndt K, Bozdagi O, Shapiro L, Huntley GW, Benson DL, Colman DR. Molecular modification of N-cadherin in response to synaptic activity. Neuron 2000,25:93-107.
12. Togashi H, Abe K, Mizoguchi A, Takaoka K, Chisaka O, Takeichi M. Cadherin regulates dendritic spine morphogenesis. Neuron, 2002, 35:77-89.
13. Parent JM, Yu TW, Leibowitz DH, Geschwind DH, Sloviter RS, Lowenstein DH. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus.J Neurosci, 1997,17;3727-3738.
14. Parent JM, Tada E, Fike JR, Leibowitz DH. Inhibition of dentate grandule cell neurogenesis with brain irradiation dose not prvent seizure induced mossy fiber synaptic reorganization in the rat. J Neurosci, 1999, 19; 4508-4519.
15. Bendotti C, Pende M, Samanin R. Expression of GAP-43 in the gransule cells of rats hippocampus after seizure-induced sprouting of mossy fiber in situ hybridization and chemical studies.Eur J Neurosci,1994,6;509-515.
16. Redies C. Cadherins and the formation of neural circuity in the vertebrate CNS.Cell Tissue Res,1997,290;405-413.
17. Brose N. Synaptic cell adhesion proteins and synaptogenesis in the mammalian central nerous system. Naturwissenschaften, 1999, 86; 516-524.
18. Tepass U, Truong K, Godt D, Ikura M, Peifer M. Cadherin in embryonic and neural morphogenesis.Nat Rev Mol Cell Boil,2000,1;91-100.
19. Lee CH, Herman T, Clandinin TR, Zipursky SL. N-cadherin regulates target specificity in the Drosophila visual system. Neuron, 2001, 30:437-450.
20. Treubert-Zimmermann U, Heyers D, Redies C. Targeting axons to specific fiber tracts in vivo by altering cadherin expression. J Neurosci, 2002,22:7617-7626.
21. Masai I, Lele Z, Yamaguchi M, Komori A, Nakata A, Nishiwaki Y, Wada H, Tanaka H, Nojima Y, Hammerschmidt M, Wilson SW, Okamoto H. N-cadherin mediates retinal lamination, maintenance of forebrain compartments and patterning of retinal neuritis. Development, 2003,130:2479-2494.
1 韩济生主编。神经科学原理(下册)。北京：北京医科大学出版社，第2版。1993：1088-1089。
2 鞠躬主编。神经生物学。北京：人民卫生出版社，第1版。2004：608-621。
3 Prince DA. Physiological mechanisms of focal epileptogenesis. Epile psia 1985;26(suppl1):S3.
4 Dudley S, Dinnera, Silvia Nemea, Dileep Nair et al. EEG and evok ed potential recording from the subthalamic nucleus for deep brain stimulation of intractable epilepsy. Clinical Neurophysiology 113(2002);1391-1402.
5 McCormick DA, Contreras D. On the cellular and network bases of epileptic seizures. Annu Rev Physiol, 2001,63:815～846.
6 Johnston D, Amaral DG. Hippocampus. In Shepherd, GM (eds), Syn aptic organization of the brain. Oxford, New York, 1998: 417-458.
7 Gjerstad L, Andersen P, Langmoen IA, Lundervold A, Hablitz J. Sy naptic triggering of epileptiform discharges in Ca~(2+) pyramidal cells in vitro. Acta Physiol Scand 1981;113:245-252.
8 Behr J,Gloveli T, Gutierrez R,Heinemann U.Spread of low Mg~(2+) indu ced epileptiform activity from the rat entorhinal cortex to the hippo campus after kindling studied in vitro.Neurosci Lett 1996;216:41-44.
9 Andersen P, Soleng AF, Raastad M. The hippocampal lamella hypot hesis revisited. Brain Research, 2000, 886:165-171.
10 Anderson P, Bliss VP, Skrede KK. Lamellar organization of hippoca mpal excitatory pathways. Exp Brain Res, 1971,13:222-238.
11 吕国蔚主编。实验神经生物学。北京：科学出版社，第1版。2002：137-163。
12 Pumain R. Electrophysiological abnormalities in chronic epileptogeni c foci:an intracellular study.Brain Res 1981;219:445-450.
13 Andersen P, Bliss TP, Richards CD. Unit anlysis of hippocampal po pulation spikes. Exp Brain Res 1971;13:208-221.
14 Shuai J, Bikson M, Hahn PJ, Lian J, Durand DM. Ionic mechanis ms underlying spontaneous CA1 neuronal firing in Ca~(2+)-free solutio n. Biophys J 2003; 84: 2099-2111.
15 Staff NP, Jung H, Thiagarajan T, et al. Resting and active propertie s of pyramidal neurons in subiculum and CA1 of rat hippocampus. J Neurophysiol, 2000,84:2398-2408.
16 Bear J, Fountain NB, Lothman EW. Responses of the superficial en torhinal cortex in slices from naive and chronically epileptic rats. J neurophysiol, 1996,76(5):2928.
17 Rafiqu A, Zhang YF, Delorenzo RJ et al. Long-sustained epileptifor m activity in the hippocampal-parahippocampal slices:a model of sta tus epilepticus. J Neurophysiol,1995,74(5):2028-2029.
18 Klishin A, Tsintsadze T, Lozovaya N, Krishtal O. Latent N-methyl-D-aspartate receptors in the recurrent excitatory pathway between hi ppocampal CA1 pyramidal neurons: Ca~(2+)-dependent activation by bl oking A_1 adonosine receptors. Proc Natl Acad Sci 1995; 92: 12431-12435.
19 Bazan NG, Tu B, Rodriguez DT, Elena B. What synaptic lipid sign aling tells us about seizure-induced damage and epileptogenesis. Pro g Brain Res 2002; 135: 175-185.
20 Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr 2000; 130: 1007S-1015S.
21 Mathern GW, Babb TL, Armstrong DL. Hippocampal sclerosis. In:E ngel J, Pedley TA,eds. Epilepsy: a comprehensive textbook. Philadel phia: Lippincott-Raven Publishers, 1997:137-149.
22 Lothman EW, Bertram EH. Epileptogenic effects of status epileptica. Epilepsia,1993, 34 Suppl: S59-70.
23 Mikati M. Neuronal cell death in a rat model of mesial temporal lo be epilepsy is induced by the initial status epilepticus and not by later repeated spontaneous seizures. Epilepsia, 2004, 45(3): 296-297.
24 Shetty AK, Turner DA. Fetal hippocampal cells grafted to kainate lesioned CA3 region of adult hippocampus suppress aberrant.supragra nular sprouting of host mossy fibers.Exp Neurol, 1997, 143 (2):231-245.
1. Wiebe S, Blume WT, Girvin JP et al. A randomiomized, controlled trial of surgery for temporal lobe epilepsy. N Engt J Med,2001 , 345(5):311-318.
2. Schwartzkroin PA. In Epilepsy: models, mechanisms, and concepts. Edited by Schwartzkroin PA. 1993, London, Cambridge University Press, pp: 1-18.
3. Stables JP, Bertram EH, White HS, Coulter DA, Dichter MA, Jacobs MP, Loscher W, Lowenstein DH, Moshe SL, Noebels JL and Davis M. Models for epilepsy and epileptogenesis: report from the NIH workshop, Bethesda, Maryland. Epilepsia 2002; 43:1410-1420.
4. Borges K, Gearing M, McDermott GD et al. Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model.Experimental Neurology, 2003,182(1):21-34.
5. Elger CE. Epilepsy:A model for the study of brain function. Lancet Neural, 2005, 4(1):3-5.
6. Epilepsy Foundation of America Working Group on Status Epilepticus. Treatment of convulsive status epilepticus. JAMA 1993;270: 854-859.
7. Sperk G Kainic acid seizures in the rat. Progr Neurobiol, 1994,42: 1-32.
8. Lothman EW, Bertram EH. Epileptogenic effects of status epileptica. Epilepsia, 1993, 34 Suppl: S59-70.
9. Mohdin R, Robert E, Sompong S, et al. Evidence that injury-induced changes in hippocampal neuronal calcium dynamics during epileptogenesis cause acquired epilepsy. Proceedings of the National Academy of Science of the USA(PNAS), 2004, 101:17522-17527.
10. Coulter DA. Chronic epileptogeoic cellular alterations in the limbic system after status epilepticus. Epilepsia, 1999, 40(suppl 1):S23-33.
11. Goddard GV. The development of epileptic seizures through brain . stimulation at low intensity. Nature 1967; 214:1020-1021.
12. McIntyre DC, Poulter MO, Gilby K. Kindling: some old and some new. Epilepsy Res 2002; 50: 79-92.
13. Goddard GV, Mclntyre DC, Leech CK. A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol 1969; 25: 295-330.
14. Bradford HF, Peterson DW. Current views of the pathobiochemistry of epilepsy. Mol Aspects Med 1987; 9: 19-172.
15. Racine RJ. Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalography and Clinical Neurophysiology 1972b; 32: 281-294.
16. Vreugdenhil M, Wadman WJ. Potassium currents in isolated CA1 neurons of the rat after kindling epileptogenesis Neuroscience 1995; 66: 805-813.
17. Racine RJ. Modification of seizure activity by electrical stimulation. I. After-discharge threshold. Electroencephalography and Clinical Neurophysiology 1972a; 32: 269-279.
18. Markram H, Sakmann B. Calcium transients in dendrites of neocortical neurons evoked by single subthreshold excitatory postsynaptic potentials via low-voltage-activated calcium channels. Proc natl Acad Sci USA 1994; 91:5207-5211.
19. Lisman E Goldring MA. Feasibility of long-term storage of graded information by the Ca~(2+)/calmodulin-dependent protein kinase molecules of the postsynaptic density. Proc natl Acatl Sci USA 1988; 85:5320-5324.
20. Miyakawa H, Ross WN, Jaffe DB, Callaway JC, Lasser-Ross N, Lisman JE, Johnston D. Synaptically activated increases in Ca~(2+) concentration in hippocampal CA1 pyramidal cells are primarily due to voltage-gated Ca~(2+) channels. Neuron 1992; 9: 1163-1173.
21. Regehr WG, Tank DW. Calcium concentration dynamics produced by synaptic activation of CAl hippocampal pyramidal cells. J Neurosci 1992;12:4202-4223.
22. Takahashi K, Wakamori M, Akai N. Hippocampal CAl pyramidal cells of rats have four voltage-dependent calcium conductances. Neurosci Lett 1989; 104: 229-234.
23. Carbone E, Lux HD. Kinetics of a low-voltage-activated calcium current in chick and rat sensory neurones. J Physiol 1987; 386: 547-570.
24. Jefferys GR. Basic mechanisms of focal epilepsy. Expl Physiol 1990; 75: 127-162.
25. Dawson RJ, Wallace DR. Kainic acid induced seizures in aged rats: neurochemical correlates. Brain Res Bull, 1992,29:45-566.
26. Holtmaat AJ, Goiter JA, De Wit J et al. Transient down regulation of Sema3A mRNA in a rat model for temporal lobe epilepsy. a novel molecular event potentially contributing to mossy fiber sprouting. Exp Neurol, 2003,182:142-150.
27. Sawamura A, Hashizume K, Yoshida K and Tanaka T. Kainic acid-induced substantia nigra seizure in rats: behavior, EEG and metabolism. Brain Research 2001 ;911:89-95.
28. Gorter JA, Goncalves PM, Vliet EA, et al. Neuronal cell death in a rat model for temporal lobe epilepsy is induced by the initial status epilepticus and not by later repcated spontaneous seizures. Epilepsia, 2003,44:647-658.
29. Leite JP, Bortolotto ZA, Cavalheiro EA. Spontaneous recurrent seizures in rats: an experimental model of partial epilepsy. Neurosci Biobehav Rev 1990; 14: 511-517.
30. Westbrook GL. Glutamate receptor update. Curr Opin Neurobiol 1994; 4: 337-346.
31. Coan EJ, Saywood W, Collingridge GL. MK-801 blocks NMDA receptor mediated synaptic transmission and long term potentiation in rat hippocampal slices. Neurosci Lett 1987; 80:111-114.
32. Collingridge GL, Kehl SJ, McLennan H. Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. J Physiol (London) 1983;334: 33-46.
33. Bliss TBP, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus (review). Nature 1993;361:31-39.
34. Tromner BL, Pasternak JF. NMDA receptor antagonists inhibit kindling epileptogenesis and seizure expression in developing rats. Dev Brain Res 1990; 53: 248-252.
35. Gilbert. Potentiation of inhibition with perforant path kindling: an NMDA-receptor dependent process. Brain Res 1991;564:109-116.
36. Yeh GC, Bonhaus DW, Nadler JV, McNamara JO. N-methyl-D-aspartate receptor plasticity in kindling: quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex. Proc Natl Acad Sci USA 1989; 86: 8157-8160.
37. McNamara JO, Russell RD, Rigsbee L, Bonhaus DW. Anti-convulsant and antiepileptogenic actions of MK-801 in kindling and electroshock models. Neuropharmacology 1988; 27:563-568.
38. Mody I, Heinemann U. NMDA receptors of dentate gyrus granule cells participate in synaptic transmission following kindling. Nature 1987; 326: 701-704.
39. Sutula T, Koch J, Golarai G, Watanabe Y, McNamara JO. NMDA receptor dependence of kindling and mossy fiber sprouting: evidence that the NMDA receptor regulates patterning of hippocampal circuits in the adult brain. J Neurosci 1996; 16:7398-7406.
40. Panchision DM, Gerwin CM, DeLorenzo RJ, Jakoi ER. Glutamate receptor activation regulates mRNA at both transcriptional and posttranscriptional levels. J Neurochem 1995:65: 969-977.
41. Perlin JB, Gerwin CM, Panchision DM, Vick RS, Jakoi ER, DeLorenzo RJ. Kindling produces long-lasting and selective changes in gene expression of hippocampal neurons. Proc Natl Acad Sci USA 1993; 90: 1741-1745.
42. Cavalheiro EA, Leite JP, Bortolotto ZA, Turski WA, lkonomidou C, Turski L. Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia 1991;32:778-782.
43. Mikati MA, Werner S, Gatt A, Liu Z, Rahmeh AA, Rachid RA, Stafstrom CE, Holmes GL. Consequences of a-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid receptor blockade during status epilepticus in the developing brain. Brain Res Dev Brain Res 1999; 113: 139-142.
44. Baran H, Loscher W, Mevissen M. The glycine/NMDA receptor partial agonist D-cycloserine blocks kainate-induced seizures in rats. Comparison with MK-801 and diazepam. Brain Res 1994; 652: 195-200.
45. MacGregor DG, Graham DI, Stone TW. The attenuation of kainate-induced neurotoxicity by chlormethiazole and its enhancement by dizocilpine, muscimol, and adenosine receptor agonists. Exp Neurol 1997; 148: 110-123.
46. Marinho MM, Sousa FC, Bruin VM, Vale MR, Viana GS. Effects of lithium, alone or associated with pilocarpine, on muscarinic and dopaminergic receptors and on phosphoinositide metabolism in rat hippocampus and striatum. Neurochem. Int, 1998, 33: 299-306.
47. Savolainen KM, Hirvonen MR. Second messengers in cholinergic-induced convulsions and neuronal injury. Toxicol Lett, 1992, 64: 437-445.
48. Einet H, Kofman O, Itkin O, et al. Augmentation of lithium's behavioral effect by inositol uptake inhibitors. J Neural Transrn, 1998,105:31-38.
49. Clifford DB, Olney LW, Maniotis A, et al. The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures. Neuroscience, 1987,23:953-968.
50. Clifford DB, Olney LW, Maniotis A, et al. The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures. Neuroscience, 1987,23:953-968.
51. Ormandy GC, Jope RS, Snead OC. Anticonvulsant actions of MK-801 in the lithium-pilocarpine model of status epilepticus in rats. Exp Neurol, 1989,106:172-180.
52. Coulter DA. Chronic epileptogeoic cellular alterations in the limbic system after status epilepticus. Epilepsia, 1999,40(suppl 1):S23-33.
1．张守信，金连弘。主编。神经生物学。北京：科学出版社，第1版。2002：537-591。
2. Levitan IB, Kaczmarek LK. The Neuron:Cell and Molecular Biology. 2nd ed. New York: Oxford University Press. 1997:373-467.
3. Sanes JR, Lichtman JW. Development of the vertebrate neuromuscular junction. Annu Rev Neurosci, 1999,22:389-442.
4. Smith SJ. Neuronal cytomechanics: the actin-based motility of growth cone. Science, 1988, 242:708-711.
5. Levitan IB, Kaczmarek LK. The Neuron:Cell and Molecular Biology. 2nd ed. New York: Oxford University Press. 1997:373-467.
6. N Uchida, Y Honjo, KR Johnson, MJ Wheelock and M Takeichi. The catenin/cadherin adhesion system is localized-in synaptic junctions bordering transmitter release zones. J cell Biol,1996;135(3):767-779.
7. Jun-ichiro Tsutsui, Maiko Moriyama, Naomichi Arima, Hindeo Ohtsubo, Hiromitsu Tanaka, and Massyuki Ozawa. Expression of Cadherin-Catenin Complexes in Human Leukemia Cell Lines. J. Biochem. (Tokyo), November 1996; 120:1034 - 1039.
8. Marie PJ, Debiais F, Hay E. Renulation of human cranial osteoblast phenotype by FGF-2, FGFR-2 and BMP-2 signalinng. J. Histol Histopathol, 2002, 17(3):877-885.
9. Tanaka H, Shan W, Phillips GR, Amdt K, Bozdagi O, Shapiro L, Huntley GW, Benson DL, Colman DR. Molecular modification of N-cadherin in response to synaptic activity. Neuron 2000, 25:93-107.
10. Togashi H, Abe K, Mizoguchi A, Takaoka K, Chisaka O, Takeichi M. Cadherin regulates dendritic spine morphogenesis. Neuron, 2002, 35:77-89.
11. Lee CH, Herman T, Clandinin TR, Zipursky SL. N-cadherin regulates target specificity in the Drosophila visual system. Neuron, 2001, 30:437-450.
12. Treubert-Zimmermann U, Heyers D, Redies C. Targeting axons to specific fiber tracts in vivo by altering cadherin expression. J Neurosci, 2002,22:7617-7626.
13. Masai I, Lele Z, Yamaguchi M, Komori A, Nakata A, Nishiwaki Y, Wada H, Tanaka H, Nojima Y, Hammerschmidt M, Wilson SW, Okamoto H. N-cadherin mediates retinal lamination, maintenance of forebrain compartments and patterning of retinal neuritis. Development, 2003,130:2479-2494.
14. Orsulic S, Huber O, Aberle H, et al. E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation. J Cell Sci, 1999,112:1237-1245.
15. Daniel JM, Reynolds AB. The catenin p120(ctn) interacts with kaiso, a novel BTB/POZ domain zinc finger transcription factor. Mol Cell Biol, 1999,19:3614-3623.
16. Imamura Y, Itoh M, Maeno Y, et al. Functional domains of alpha-catenin required for the strong state of cadhein based cell adhesion. J Cell Biol, 1999,144:1311-1322.
17. Hegland DD, Sullivan DM, Rovira H, et al. Regulation of endothelial cell adherens junctions by a ras dependent singal transduction pathway. Biochem Biophys Res commun,1999,260:371-376.
18. Ozawa M, Kemler R. Altered cell adhesion activity by pervanadate due to the dissociation of alpha-catenin from the E-cadherin-catenin complex. J Biol Chem, 1998,273:6166-6170.
19. Le TL, Yap AS, Stow JL. Recycling of E-caherin:a potential mechanism for regulating cadherin dynamics. J Cell Biol,1999,13:362-378.