跳到主要內容

臺灣博碩士論文加值系統

(3.236.124.56) 您好!臺灣時間:2021/07/31 04:16
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:江嘉駒
研究生(外文):Chia-ChuChiang
論文名稱:高頻電刺激抑制癲癇之研究
論文名稱(外文):Study of A Seizure Suppression System by Using High Frequency Electrical Stimulation
指導教授:朱銘祥朱銘祥引用關係
指導教授(外文):Ming-Shaung Ju
學位類別:博士
校院名稱:國立成功大學
系所名稱:機械工程學系碩博士班
學門:工程學門
學類:機械工程學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:英文
論文頁數:140
中文關鍵詞:4-AP高頻刺激海馬回模型lithium-pilocarpine開關控制癲癇抑制
外文關鍵詞:4-APhigh frequency stimulationhippocampal modellithium-pilocarpineon-off controlseizuresuppression
相關次數:
  • 被引用被引用:0
  • 點閱點閱:116
  • 評分評分:
  • 下載下載:3
  • 收藏至我的研究室書目清單書目收藏:1
癲癇是常見神經系統疾病之一,其主要的特徵為腦部不正常放電。目前癲癇普遍的治療方式是服用抗癲癇藥物和手術切除癲癇病灶區域。雖然癲癇藥物持續蓬勃發展,但仍有三分之一的癲癇病患無法依靠藥物治療,因此,開始有研究人員嘗試發展其它如電刺激的治療方式。高頻電刺激對於癲癇控制具有發展的潛力。雖然利用高頻電刺激治療癲癇的機轉不是很清楚,但已經有動物實驗與臨床試驗的結果指出高頻電刺激有效於癲癇的抑制或是癲癇發作頻率的減少。因此,本研究乃是要用高頻電刺激來達到癲癇控制的效果。首先,探討電刺激強度與電刺激位置對於癲癇波的影響,找尋合適的電刺激參數。接著根據研究成果整合開關控制的閉回路控制系統來改善高頻電刺激的缺點與增進電刺激的效率。最後,本研究亦建立一個具有生理基礎的數學模型,藉由癲癇波的模擬來探討癲癇發作的原因以及高頻電刺激抑制癲癇的可能機轉。
本研究利用了兩種動物癲癇模型來進行相關實驗。一為lithium-pilocarpine藥物誘發,另一項為4-AP藥物誘發。在癲癇抑制的實驗中所利用的動物模型是4-AP藥物誘發。在實驗設計上,一者是利用開回路電刺激方式來研究電刺激的最佳參數,另一項則是利用閉回路控制來達到更有效的癲癇抑制效果。在開回路電刺激的實驗中,6個記錄用電極分別植入到海馬回內去研究電刺激在海馬回內空間上的效果。2個電刺激電極則是各別植入到海馬聯合以及癲癇病灶位置來研究不同電刺激區域對癲癇抑制的效果。在閉回路控制電刺激的實驗中,高頻電刺激整合了開關控制器來改善電刺激效率。開關控制電刺激所設定的癲癇抑制時間是20 秒,而開關控制電刺激的效率則是經由電刺激時間、累積電量、刺激後抑制時間來評估。最後,一個具有生理基礎的海馬回數學模型藉由模擬正常腦波與lithium-pilocarpine藥物誘發的癲癇波來解釋癲癇發作的原因。除此之外,此模型經過適當的修改,也可以用來模擬電刺激的效果並推測相關的機轉,也可以用來模擬開關控制電刺激的結果與分析開關控制器的穩定性。
本研究結果顯示海馬聯合與病灶區域的電刺激都能產生抑制癲癇的效果,而電刺激的強度與癲癇抑制的成功率具有正相關。然而,本研究亦發現電刺激會產生副作用,亦即是癲癇波的轉換並延長癲癇發作時間。癲癇波的轉換與電刺激強度具有正相關而且病灶區域的電刺激比海馬聯合電刺激更容易誘發出癲癇波的轉換。而開關控制電刺激能夠有效的延長癲癇抑制的效果。除此之外,在整合開關控制器之後,減少每段電刺激的時間長度可以降低總電刺激的時間,減少電刺激的累積電量,增加刺激後抑制的時間。最後,本研究提出的海馬回模型也成功地藉由改變模型的參數來模擬出正常腦波、癲癇波、與高頻電刺激的效果。而模型參數改變所代表的生理意義也和文獻上利用動物實驗所得到的結果相吻合。
總結來說,本研究結論有三。一是海馬聯合與病灶區域的電刺激都能產生抑制癲癇的效果但若要考慮何者為最佳電刺激參數時還得要考慮電刺激所引發的副作用。二是開關控制電刺激不但成功延長抑制癲癇的時間也避免了高頻電刺激副作用的產生。此外,當高頻電刺激整合開關控制器之後,減少每次電刺激的時間能夠有效的改善電刺激的效率。最後,本研究模擬所得到的結果能夠推測出與前人實驗所得到的相關結論。
Epilepsy is one of common neurological disorders and characterized by epileptic seizures. The popular treatments of epilepsy are antiepileptic drugs and surgical resection of epileptic focus. With development of antiepileptic drugs, there are still one third of patients suffering from seizures. Therefore, researchers try to find alternative treatments for seizure control, such as electrical stimulation. High frequency electrical stimulation is a potential therapy for seizure control. Although the mechanisms of curing epilepsy by high frequency stimulation are unclear, many animal experiments and clinical trials have shown that high frequency stimulation is effective in seizure suppression or reduction of seizure frequency. Therefore, this study is to use high frequency stimulation for seizure control. The best parameters of high frequency stimulation including stimulation locations and amplitudes are investigated. Furthermore, the efficiency and the drawbacks of the high frequency stimulation are improved by closed-loop control stimulation. Finally, a physiologically computational model is established for interpreting the possible mechanisms of seizure progression and seizure suppression by high frequency stimulation.
Two kinds of epileptic animal models are induced and characterized. One is lithium-pilocarpine model and the other is 4-AP model. The experiments of seizure suppression are done in the 4-AP model based on the setting of open-loop stimulation and closed-loop stimulation. In the experiments of open-loop stimulation, six recording electrodes are implanted in the hippocampus to explore the spatial effects of stimulation. Two stimulation electrodes are implanted in the commissural tract and focus site to compare the effects of high frequency stimulation on different sites. In the experiments of closed-loop stimulation, on-off control algorithm is integrated to improve the efficiency and drawbacks of high frequency stimulation. On-off control stimulation is used to suppress the 4-AP induced seizures in 20-second intervals. The stimulation time, cumulative charge and post-stimulation suppression were used to assess the effects of burst duration. Finally, a physiologically-based hippocampal model is used to simulate the normal neural activity and epileptic activity induced by the lithium-pilocarpine treatment to explain the seizure progression. The hippocampal model is also modified to simulate the effects of high frequency stimulation and on-off control stimulation to interpret the possible mechanism and stability of the on-off controller.
The results show that both tract and focus site stimulation could generate seizure suppression. The suppression rates are dependent on the stimulation amplitude. However, high frequency stimulation also causes the side effect, conversion of the seizure patterns. The conversion rates increase with higher stimulation amplitudes and are higher with focus site stimulation. On-off control stimulation could prolong the effect of seizure suppression and the shorter burst duration could keep the seizure suppressed with less effort. By decreasing the burst duration, cumulative stimulation time becomes shorter, the delivered cumulative charge becomes lower, and the cumulative time of post-stimulation suppression becomes longer. Model simulation shows that normal neural activity, epileptic activity, and the effects of high frequency stimulation can be simulated by adjusting the model parameters. The changes of the parameters in the model are compatible and similar with the experimental results in the literature.
To conclude, both tract and focus site stimulation can produce global suppression of hippocampus and the choice of stimulation parameters is critical in order to produce suppression, but conversion of seizure pattern. Secondly, on-off control stimulation not only prolongs the duration of suppression but also avoids the side effect of the conversion of seizure patterns. In particular, decreasing the burst duration increases the efficiency of the burst stimulation. Finally, model simulation suggests the support of the possible mechanisms, based on the experimental results reported in the literature.
摘要 i
Abstract iii
誌謝 vi
Contents vii
List of Figures xii
List of Tables xxii
Nomenclatures xxiii
1. Introduction 1
1.1. Introduction of seizures and epilepsies 1
1.2. Hippocampal physiology 5
1.3. Animal seizure models 10
1.4. Electrical stimulation for seizure control 12
1.5. Computational model of cerebral circuit 15
1.6. Objectives 17
2. Methods 19
2.1. Recording systems for neural activity 19
2.1.1. The stereotaxic surgery 19
2.1.2. Bilateral hippocampal recording in freely moving rats 20
2.1.3. Global hippocampal recording in anesthetized rats 22
2.2. Electrical stimulation system 26
2.3. Induction of seizures 27
2.3.1. Lithium-pilocarpine induced seizure 27
2.3.2. 4-AP induced seizure 28
2.4. Removal of stimulation artifacts 29
2.4.1. Algorithm formulation 29
2.4.2. Validation experiment of the algorithm 30
2.5. Open-loop stimulation for seizure suppression 31
2.5.1. Experimental setup 31
2.5.2. Stimulation parameters 32
2.5.3. Quantification of seizure suppression and statistical analyses 33
2.6. Closed-loop stimulation system for seizure suppression (On-off control) 34
2.6.1. Experimental setup 34
2.6.2. Spike detection algorithm 35
2.6.3. Stimulation parameters and implementation of on-off control 38
2.6.4. Quantification of efficiency of on-off control stimulation 41
2.7. Construction of simulation models 42
2.7.1. Hippocampal model 42
2.7.2. Modified hippocampal model 47
2.8. Applications of simulation model 50
2.8.1. Simulating the whole course of status epilepticus 50
2.8.2. Simulating the on-off control stimulation 52
2.8.3. Stability analysis of the on-off controller 53
3. Results 56
3.1. Neural activity and behaviors of the animal seizure models 56
3.1.1. Low dose lithium-pilocarpine model 56
3.1.2. 4-AP model 60
3.2. Validation of stimulation artifact removal algorithm 64
3.3. Effects of high frequency stimulation (Open-loop) 66
3.3.1. Seizure suppression by high frequency stimulation 66
3.3.2. Spatial extent of suppression by tract or focus site stimulation 71
3.3.3. Conversion of seizure pattern by high frequency stimulation 75
3.4. Seizure control by on-off stimulation system (closed-loop) 79
3.4.1. The feasibility of on-off stimulation system 79
3.4.2. Efficiency of on-off stimulation system 81
3.5. Simulation of seizure induction and seizure suppression 85
3.5.1. Simulation of lithium-pilocarpine induced seizure 85
3.5.2. Simulation of the effects produced by high frequency stimulation 94
3.5.3. Stability analysis of on-off controller 97
3.5.4. Simulation of on-off stimulation system 98
4. Discussion 104
4.1. Characteristics of the animal seizure models 104
4.1.1. Characteristics of low dose lithium-pilocarpine model 104
4.1.2. Characteristics of 4-AP model 105
4.2. Tract stimulation and focus site stimulation in the open-loop system 108
4.3. Possible mechanisms of seizure suppression by high frequency stimulation 111
4.4. Applicability of model simulation 113
4.4.1. Applicability of the hippocampal model to the seizure model 113
4.4.2. Interpretation of seizure progression from model simulation 117
4.4.3. Interpretation of seizure suppression from model simulation 120
4.5. The advantages and drawbacks of on-off closed-loop stimulation system 123
4.5.1. The features of on-off control stimulation 123
4.5.2. The drawbacks of the on-off control stimulation 125
5. Conclusions 127
5.1. Conclusions 127
5.2. Contribution 128
5.3. Future works 129
References 131
References
[1] Commission on Classification and Terminology of the International League Against Epilepsy, Proposal for revised clinical and electroencephalographic classification of epileptic seizures, Epilepsia, 22: 489-501, 1981.
[2] Commission on Classification and Terminology of the International League Against Epilepsy, Proposal for revised classification of epilepsies and epileptic syndromes, Epilepsia, 30: 389-399, 1989.
[3] S. Shinnar, C. O'Dell, and A. T. Berg, Distribution of epilepsy syndromes in a cohort of children prospectively monitored from the time of their first unprovoked seizure, Epilepsia, 40: 1378-1383, 1999.
[4] H. G. Wieser, Mesial temporal lobe epilepsy with hippocampal sclerosis: Report of the commission on Neurosurgery, Epilepsia, 45: 695-714, 2004.
[5] T. F. Freund, and G. Buzsaki, Interneurons of the hippocampus, Hippocampus, 6: 347-470, 1996.
[6] G. Curia, et al., The pilocarpine model of temporal lobe epilepsy, Journal of Neuroscience Methods, 172: 143-157, 2008.
[7] F. O. Scorza, et al., The pilocarpine model of epilepsy: what have we learned?, Annals of the Brazilian Academy of Sciences, 81: 345-365, 2009.
[8] N. Y. Walton, and D. M. Treiman, Response of status epilepticus induced by lithium and pilocarpine to treatment with diazepam, Experimental Neurobiology 101: 267-275, 1988.
[9] E. Hirsch, T. Z. Baram, and O. C. S. III, Ontogenic study of lithium-pilocarpine-induced status epilepticus in rats, Brain Research, 583: 120-126, 1992.
[10] R. Sankar, et al., Patterns of status epilepticus-induced neuronal injury during development and long-term consequences, The Journal of Neuroscience, 18: 8382-8393, 1998.
[11] J. François, E. Koning, A. Ferrandon, and A. Nehlig, The combination of topiramate and diazepam is partially neuroprotective in the hippocampus but not antiepileptogenic in the lithium-pilocarpine model of temporal lobe epilepsy, Epilepsy Research, 72: 147-163, 2006.
[12] F. Pena, and R. Tapia, Seizures and neurodegeneration induced by 4-amniopyridine in rat hippocampus in vivo: role of glutamate- and GABA-mediated neurotransmission and of ion channels, Neuroscience, 101: 547-561, 2000.
[13] E. D. Martin, and M. A. Pozo, Valproate suppresses status epilepticus induced 4-amniopyridine in CA1 hippocampus region, Epilepsia, 44: 1375-1379, 2003.
[14] X. Yang, and S. M. Rothman, Focal cooling rapidly terminates experimental neocortical seizures, Annals of Neurology, 49: 721-726, 2001.
[15] S. Nadkarni, J. LaJoie, and O. Devinsky, Current treatments of epilepsy, Neurology, 64: 2-11, 2005.
[16] M. Morrell, Brain stimulation for epilepsy: can scheduled or responsive neurostimulation stop seizure?, Current Opinon in Neurology, 19: 164-168, 2006.
[17] Y. Li, and D. J. Mogul, Electrical control of epileptic seizure, Journal of Clinical Neurophysiology, 24: 197-204, 2007.
[18] S. Nagel, and I. M. Najm, Deep brain stimulation for epilepsy, Neuromodulation, 12: 270-280, 2009.
[19] J. Fridley, J. G. Thomas, J. C. Navarro, and D. Yoshor, Brain stimulation for the treatment of epilepsy, Neurosurgical Focus, 32: E13, 2012.
[20] X. L. Zhong, et al., Deep brain stimulation for epilepsy in clinical practice and in animal models, Brain Research Bulletin, 85: 81-88, 2011.
[21] A. L. Benabid, et al., Therapeutic electrical stimulation of the central nervous system, Comptes Rendus Biologies, 328: 177-186, 2005.
[22] C. Haman, et al., Deep brain stimulation of the anterior nucleus of the thalamus: effects of electrical stimulation on pilocarpine-induced seizures and status epilepticus, Epilepsy Research, 78: 117-123, 2008.
[23] R. Davis, Cerebellar stimulation for cerebral palsy spasticity, function, and seizures, Archives of Medical Research, 31: 290-299, 2000.
[24] F. A. Lado, L. Velisek, and S. L. Moshe, The effect of electrical stimulation of the subthalamuc nucleus on seizures is frequency dependent, Epilepsia, 44: 157-164, 2003.
[25] L. H. Shi, F. Luo, D. Woodward, and J. Y. Chang, Deep brain stimulation of the substantia nigra pars reticulate exerts long lasting suppression of amygdale-kindled seizures, Brain Research, 1090: 202-207, 2006.
[26] S. R. Weiss, et al., Quenching: inhibition of development and expression of amygdala kindled seizures with low frequency stimulation, Neuroreport, 6: 2171-2176, 1995.
[27] T. Wyckhuys, et al., High frequency deep brain stimulation in the hippocampus modifies seizure characteristics in kindled rats, Epilepsia, 48: 1543-1550, 2007.
[28] D. M. Durand, and M. Bikson, Suppression and control of epileptiform activity by electrical stimulation: a review, Proceedings of the IEEE, 89: 10065-1082, 2001.
[29] K. Jerger, and J. Schiff S, Periodic pacing of an in-vitro epileptic focus, Journal of Neurophysiology, 73: 876-879, 1995.
[30] J. Lian, et al., Local suppression of epileptiform activity by electrical stimulation in rat hippocampus in vitro, Journal of Physiology, 547: 427-434, 2003.
[31] P. Rajdev, M. Ward, and P. Irazoqui, Effect of Stimulus Parameters in the Treatment of Seizures by Electrical Stimulation in the Kainate Animal Model, International Journal of Neural Systems, 21: 151, 2011.
[32] C. H. Manola, N. B. Letecia, and L. R. Luisa, Behavioral effects of high frequency electrical stimulation of the hippocampus on electrical kindling in rats, Epilepsy Research, 72: 10-17, 2006.
[33] T. Wyckhuys, et al., Comparison of hippocampal deep brain stimulation with high (130Hz) and low frequency (5Hz) on afterdischarges in kindled rats, Epilepsy Research, 88: 239-246, 2010.
[34] A. L. Velasco, et al., Electrical stimulation of the hippocampal epileptic foci for seizure control: a double-blind, long-term follow-up study, Epilepsia, 48: 1895-1903, 2007.
[35] P. Boon, et al., Deep brain stimulation in patients with refractory temporal lobe epilepsy, Epilepsia, 48: 1551-1560, 2007.
[36] J. F. Tellez-Zenteno, et al., Hippocampal electrical stimulation in mesial temporal lobe epilepsy, Neurology, 66: 1490-1494, 2006.
[37] K. B. Kile, N. Tian, and D. M. Durand, Low frequency deep brain stimulation decreases seizure activity in a mutation model of epilepsy, Epilepsia, 51: 1745-1753, 2010.
[38] S. Rashid, et al., Low frequency stimulation of hippocampal commissures reduces seizures in chronic rat model of temporal lobe epilepsy, Epilepsia, 53: 147-156, 2012.
[39] A. L. Jensen, and D. M. Durand, Suppression of axonal conduction by sinusoidal stimulation in rat hippocampus in vitro, Journal of Neural Engineering, 4: 1-16, 2007.
[40] A. L. Jensen, and D. M. Durand, High frequency stimulation can block axonal conduction, Experimental Neurology, 220: 57-70, 2009.
[41] I. Osorio, et al., Automated seizure abatement in humans using electrical stimulation, annals of Neurology, 57: 258-268, 2005.
[42] C.-C. Chiang, C.-C. K. Lin, M.-S. Ju, and D. M. Durand, High frequency stimulation can suppress globally seizures induced by 4-AP in the rat hippocampus: An acute in vivo study, Brain Stimulation, 6: 180-189, 2013.
[43] F. H. L. d. Silva, A. Hoeks, H. Smits, and L. H. Zetterberg, Model of brain rhythmic activity, Kybernetik, 15: 27-37, 1974.
[44] W. J. Freeman, Model of the dynamics of neural populations, Contemporary Clinical Neurophysiology, s34: 9-18, 1978.
[45] A. V. Rotterdam, and F. H. L. D. Silva, A model of the spatial-temporal characteristics of the alpha rhythm, Bulletin of Mathematical Biology, 44: 283-305, 1982.
[46] F. H. Eeckman, and W. J. Freeman, Asymmetric sigmoid nonlinearity in the rat olfactory system, Brain Research, 557: 13-21, 1991.
[47] B. H. Jansen, G. Zouridakis, and M. E. Brandt, A neurophysiologically-based mathematical model of flash visual evoked potentials, Biological Cybernetics, 68: 275-283, 1993.
[48] B. H. Jansen, and V. G. Rit, Electroencephalogram and visual evoked potential generation in a mathematical model of coupled cortical columns, Biological Cybernetics, 73: 357-366, 1995.
[49] P. Suffczynski, S. Kalitzin, G. Pfurtscheller, and F. H. L. d. Silva, Computational model of thalamo-cortical networks: dynamical control of alpha rhythm in relation to focal attention, International Journal of Psychophysiology, 43: 25-40, 2001.
[50] C.-W. Chen, M.-S. Ju, Y.-N. Sun, and C.-C. K. Lin, Model analyses of visual biofeedback training for EEG-based brain-computer interface, Journal of Computational Neuroscience, 27: 357-368, 2009.
[51] F. L. da Silva, et al., Epilepsies as dynamical diseases of brain systems: Basic models of the transition between normal and epileptic activity, Epilepsia, 44: 72-83, 2003.
[52] P. Suffczynski, S. Kalitzin, and F. H. Lopes Da Silva, Dynamics of non-convulsive epileptic phenomena modeled by a bistable neuronal network, Neuroscience, 126: 467-484, 2004.
[53] F. Wendling, J. J. Bellanger, F. Bartolomei, and P. Chauvel, Relevance of nonlinear lumped-parameter models in the analysis of depth-EEG epileptic signals, Biological Cybernetics, 83: 367-378, 2000.
[54] F. Wendling, F. Bartolomei, J. J. Bellanger, and P. Chauvel, Epileptic fast activity can be explained by a model of impaired GABAergic dendritic inhibition, Eurpean Journal of Neuroscience, 15: 1499-1508, 2002.
[55] F. Wendling, et al., Interictal to ictal transition in human temporal lobe epilepsy: insight from a computational model of intracerebral EEG, Journal of Clinical Neurophysiology, 22: 343-356, 2005.
[56] B. A. Lopour, and A. J. Szeri, A model of feedback control for the charge-balanced suppression of epileptic seizures, Journal of Computational Neuroscience, 28: 375-387, 2010.
[57] S. N. Ching, E. N. Brown, and M. A. Kramer, Distributed control in a mean-field cortical network model: Implications for seizure suppression, Physical Review E, 86: 021920, 2012.
[58] C.-C. Chiang, M.-S. Ju, and C.-C. K. Lin, Description and computational modeling of the whole course of status epilepticus induced by low dose lithium–pilocarpine in rats, Brain Research, 1417: 151-162, 2011.
[59] G. Paxions, and C. Watso, The rat brain in stereotaxic coordinates, 6 ed.: Elsevier, 2007.
[60] F. Kloosterman, P. Peloquin, and L. S. Leung, Apical and basal orthodromic population spikes in hippocampal CA1 in vivo show different origins and patterns of propagation, Journal of Neurophysiology, 86: 2435-2444, 2001.
[61] L. D. Iasemidis, and J. C. Sackellares, Chaos theory and epilepsy, The Neuroscientist, 2: 118-126, 1996.
[62] S. J. Schiff, et al., Controlling chaos in the brain, Nature, 370: 615-620, 1994.
[63] G. Ullah, and S. Schiff, Models of epilepsy, Scholarpedia, 4: 1409, 2009.
[64] M. I. Banks, J. A. White, and R. A. Pearce, Interactions between distinct GABAA circuits in hippocampus, Neuron, 25: 449-457, 2000.
[65] J. A. White, Networks of interneurons with fast and slow gamma -aminobutyric acid type A (GABAA) kinetics provide substrate for mixed gamma-theta rhythm, Proceedings of the National Academy of Sciences, 97: 8128-8133, 2000.
[66] L. Rankine, N. Stevenson, M. Mesbah, and B. Boashash, A nonstationary model of newborn EEG, IEEE Transactions on Biomedical Engineering, 54: 19-28, 2007.
[67] P. Celka, and P. Colditz, Nonlinear nonstationary Wiener model of infant EEG seizures, IEEE Transactions on Biomedical Engineering, 49: 556-564, 2002.
[68] W. A. Turski, et al., Limbic seizures produced by pilocarpine in rats-behavioral, electroencephalograohic and neuropathological study, Behavioural Brain Research, 9: 315-335, 1983.
[69] R. S. G. Jones, and U. Heinemann, Pre and postsynaptic K+ and Ca2+ fluxes in area CA1 of the rat hippocampus in vitro: effects of Ni2+, TEA and 4-AP Experimental Brain Research, 68: 205-209, 1987.
[70] W. Stuhmer, et al., Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain, Embo Journal, 8: 3235-3244, 1989.
[71] G. A. Gutman, et al., International union of pharmacology. LIII. nomenclature and molecular relationships of voltage-gated potassium channels, Pharmacological Reviews, 57: 473-508, 2005.
[72] B. Rudy, Diversity and ubiquity of K-channels, Neuroscience, 25: 729-749, 1988.
[73] J. F. Storm, Potassium current in hippocampal pyramidal cells, Progress in Brain Research, 83: 161-187, 1990.
[74] H. Wang, D. D. Kunkel, P. A. Schwartzkroin, and B. L. Tempel, Localization of Kv1.1 and Kv1.2, 2 K-channel proteins, to synaptic terminals, somata, and dendrites in the mouse brain, Journal of Neuroscience, 14: 4588-4599, 1994.
[75] M. Maleticsavatic, N. J. Lenn, and J. S. Trimmer, Differential spatiotemporal expression of K+ channel polypeptides in rat hippocampal neurons developing in situ and in vitro, Journal of Neuroscience, 15: 3840-3851, 1995.
[76] D. A. Hoffman, and D. Johnston, Downregulation of transient K+ channels in dendrites of hippocampal CA1 pyramidal neurons by activation of PKA and PKC, Journal of Neuroscience, 18: 3521-3528, 1998.
[77] M. Martina, et al., Functional and molecular differences between voltage-gated K+ channels of fast-spiking interneurons and pyramidal neurons of rat hippocampus, Journal of Neuroscience, 18: 8111-8125, 1998.
[78] A. E. Metz, N. Spruston, and M. Martina, Dendritic D-type potassium currents inhibit the spike afterdepolarization in rat hippocampal CA1 pyramidal neurons, Journal of Physiology-London, 581: 175-187, 2007.
[79] J. F. Storm, Temporal integration by a slowly inactivationg K+ current in hippocampal neurons, Nature, 336: 379-381, 1988.
[80] Y. Gu, S. Y. Ge, and D. Y. Ruan, Effect of 4-aminopyridine on synaptic transmission in rat hippocampal slices, Brain Research, 1006: 225-232, 2004.
[81] P. Perreault, and M. Avoli, 4-aminopyridine-induced epileptiform activity and a GABA-mediated long-lasting depolarization in the rat hippocampus, The Journal of neuroscience, 12: 104-115, 1992.
[82] C. Psarropoulou, and M. Avoli, Developmental features of 4-aminopyridine induced epileptogenesis, Developmental Brain Research, 94: 52-59, 1996.
[83] W. P. Chang, et al., Spatiotemporal organization and thalamic modulation of seizures in the mouse medial thalamic-anterior cingulate slice, Epilepsia, 52: 2344-55, 2011.
[84] G. D'Arcangelo, G. Panuccio, V. Tancredi, and M. Avoli, Repetitive low-frequency stimulation reduces epileptiform synchronization in limbic neuronal networks, Neurobiol Dis, 19: 119-28, 2005.
[85] J. Nissinen, T. Halonen, E. Koivisto, and A. Pitkanen, A new model of chronic temporal lobe epilepsy induced by electrical stimulation of the amygdale in rat, Epilepsy Research, 38: 177-205, 2000.
[86] J. L. Hellier, et al., Assessment of inhibition and epileptiform activity in the septal dentate gyrus of freely behaving rats during the first week after kainite treatment, The Journal of Neuroscience, 19: 10053-10064, 1999.
[87] T. Wyckhuys, et al., Hippocampal deep brain stimulation induces decreased rCBF in the hippocampal formation of the rat, Neuroimage, 52: 55-61, 2010.
[88] C. C. McIntyre, W. M. Grill, D. L. Sherman, and N. V. Thakor, Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition, Journal of Neurophysiology, 91: 1457-1469, 2004.
[89] C. Beurrier, B. Bioulac, J. Audin, and C. Hammond, High-frequency stimulation produces a transient blockade of voltage-gated currents in subthalamic neurons, Journal of Neurophysiology, 85: 1351-1356, 2001.
[90] Y. Schiller, and Y. Bankirer, Cellular Mechanisms Underlying Antiepileptic Effects of Low- and High-Frequency Electrical Stimulation in Acute Epilepsy in Neocortical Brain Slices In Vitro, Journal of Neurophysiology, 97: 1887-1902, 2007.
[91] H. Luna-Munguía, et al., Effects of hippocampal high-frequency electrical stimulation in memory formation and their association with amino acid tissue content and release in normal rats, Hippocampus, 22: 98-105, 2012.
[92] H. Luna-Munguia, S. Orozco-Suarez, and L. Rocha, Effects of high frequency electrical stimulation and R-verapamil on seizure susceptibility and glutamate and GABA release in a model of phenytoin-resistant seizures, Neuropharmacology, 61: 807-814, 2011.
[93] J. R. Smith, et al., Closed-loop stimulation in the control of focal epilepsy of Insular origin, Stereotactic and Functional Neurosurgery, 88: 281-287, 2010.
[94] N. Ishizuka, J. Weber, and D. G. Amaral, Organization of intrahippocampal projections originating from CA3 pyramidal cells in the rat, The Journal of Comparative Neurology, 295: 580-623, 1990.
[95] A. B. Kibler, and D. M. Durand, Orthogonal wave propagation of epileptiform activity in the planar mouse hippocampus in vitro, Epilepsia, 52: 1590-1600, 2011.
[96] M. R. Priel, and E. X. Albuquerque, Short-term effects of pilocarpine on rat hippocampal neurons in culture, Epilepsia, 43: 40-46, 2002.
[97] T. Nagao, A. Alonso, and M. Avoli, Epileptiform activity induced by pilocarpine in the rat hippocampal-entorhinal slice preparation, Neuroscience, 72: 399-408, 1996.
[98] I. Smolders, et al., NMDA receptor-mediated pilocarpine-induced seizures Characterization in freely moving rats by microdialysis, British Journal of Pharmacology, 121: 1171-1179, 1997.
[99] R. M. Freitas, et al., Pilocarpine-induced status epilepticus in rats: lipid peroxidation level, nitrite formation, GABAergic and glutamatergic receptor alterations in the hippocampus, striatum and frontal cortex, Pharmacology Biochemistry and Behavior, 78: 327-332, 2004.
[100] R. M. Freitas, The evaluation of effects of lipoic acid on the lipid peroxidation, nitrite formation and antioxidant enzymes in the hippocampus of rats after pilocarpine-induced seizures, Neuroscience Letters, 455: 140-144, 2009.
[101] Y. Fujiwara-Tsukamoto, et al., Prototypic Seizure Activity Driven by Mature Hippocampal Fast-Spiking Interneurons, Journal of Neuroscience, 30: 13679-13689, 2010.
[102] Z. J. Zhang, et al., Transition to Seizure: Ictal Discharge Is Preceded by Exhausted Presynaptic GABA Release in the Hippocampal CA3 Region, Journal of Neuroscience, 32: 2499-2512, 2012.
[103] S.-F. Liang, et al., Closed-loop seizure control on epileptic rat models, Journal of Neural Engineering, 8: 045001, 2011.
[104] T. S. Nelson, et al., Closed-loop seizure control with very high frequency electrical stimulation at seizure onset in the gaers model of absence epilepsy, International Journal of Neural Systems, 21: 163, 2011.
[105] M. E. Colpan, Y. Li, J. Dwyer, and D. J. Mogul, Proportional feedback stimulation for seizure control in rats, Epilepsia, 48: 1594-1603, 2007.
[106] P. J. Hahn, and D. M. Durand, Bistability dynamics in simulations of neural activity in high-extracellular-potassium conditions, Journal of Computational Neuroscience, 11: 5-18, 2001.
[107] A. Jahangiri, and D. M. Durand, Phase resetting analysis of high potassium epileptiform activity in CA3 region of the rat hippocampus, International Journal of Neural Systems, 21: 127-138, 2011.
連結至畢業學校之論文網頁點我開啟連結
註: 此連結為研究生畢業學校所提供,不一定有電子全文可供下載,若連結有誤,請點選上方之〝勘誤回報〞功能,我們會盡快修正,謝謝!
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文
 
1. 胡興梅(2001)。〈人權教育天龍八式〉。《臺灣教育》。611,54-59。
2. 林佳範(2001)。〈論人權理念與教改理念的一致性:從法治教育的言教與身教說起〉。《臺灣教育》,11,34-45。
3. 洪泉湖(2008)。〈從多元文化教育談公民素養〉。《教師天地》,157: 34-39。
4. 吳英長(1979)。〈怎麼跟小朋友講故事〉。國教之聲,13(2),1-5。
5. 林孟皇、陳叡智(1998)。〈談國小法治教育之推展〉。《研習資訊》,15(5),64-87。
6. 張秀雄、吳美嬌、劉秀嫚(1999)。〈合作學習在公民養成教育上的意義〉。《公民訓育學報》,8,123-152。
7. 高松景(2008)。〈「全人發展」的品格教育---跨越「知」與「行」間的鴻溝〉,《教師天地》,157, 58-61。
8. 李文政(1998)。〈兒童民主態度的發展與學校教育〉,《社會科教育學報》,1,73-95。李伯佳(1998)。〈國民小學民主法治教育面面觀〉。《臺灣教育》,568,42-49。
9. 李宗薇 (1996)。〈國小民主法治教育之課程內涵與課程實施之研究〉。《臺北師院學報》,9,19-52。
10. 簡文元(1998)。〈陶冶民主素養落實法治教育〉。《臺灣教育》,572,56-59。
11. 蕭妙香(2000)。〈國民小學法治教育之探討〉。《臺南師院學報》,33,263-289。
12. 董秀蘭,1998,〈政治教育的抉擇─為什麼〉,《公民訓育學報》第七輯,臺灣師大公訓系, 257-269。
13. 黃國峰(2004)。〈人權法治教育理念之探究--從美國公民教育中心的民主基礎系列 教材說起〉。《學生輔導》,93, 105-115。
14. 黃惟饒(1996)。〈從後工業社會的觀點透視我國公民教育新內涵〉。《人文及社會學科教學通訊》,7(2),6-19。
15. 曾慧佳(1998a)。〈美國當代社會科重要議題(師資培育、討論教學法、兩難困境等)探討〉。《美國社會科教育學會第77屆年會實錄》。國民教育,38(3),42-52。