(3.235.108.188) 您好!臺灣時間:2021/02/27 23:26
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:::

我願授權國圖
: 
twitterline
研究生:陳素芬
研究生(外文):Su-Fen Chen
論文名稱:單純疱疹病毒感染在海馬迴組織切片培養所誘發癲癇發生之機制探討
論文名稱(外文):Herpes simplex virus infection-induced epileptogenesis in organotypic hippocampal slice cultures
指導教授:許桂森許桂森引用關係
指導教授(外文):Kuei-Sen Hsu
學位類別:碩士
校院名稱:國立成功大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:163
中文關鍵詞:海馬迴組織切片培養頑固型癲癇單純疱疹病毒
外文關鍵詞:Organotypic hippocampal slice cultureHSVintractable epilepsy
相關次數:
  • 被引用被引用:1
  • 點閱點閱:329
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:33
  • 收藏至我的研究室書目清單書目收藏:0
中文摘要
(Abstract in Chinese)

癲癇是一種腦中神經元不自主放電的慢性疾病,其臨床特徵係不斷自發性的重覆發作。目前在臨床上大約有65-70%的癲癇患者,可以利用現有的抗癲癇藥物進行良好控制。然而約有25-30%對於目前抗癲癇藥物是無效的,此類的癲癇病人被統稱為「頑固型癲癇」病人。然而截至目前為止,對於頑固型癲癇發生的過程、原因及分子機制尚未清楚。因此詳盡地了解頑固型癲癇發生的原因及機制是目前在癲癇研究領域中一個相當重要且急待解決的課題。在近年來的臨床研究觀察中發現,頑固型癲癇病人在以外科手術的方法進行病兆區域切除治療時,其病兆區域的組織中通常會含有大量的第一型單純疱疹病毒DNA表現,因此推測第一型單純疱疹病毒感染與頑固型癲癇的發生過程可能有某種程度的相關性,然而其相關性為何則仍然未知。為了證明第一型單純疱疹病毒感染與頑固型癲癇的相關性,我們擬以長期性腦組織切片培養系統來進行研究模式的建立,並利用電氣生理學、組織免疫染色及組織切片觀察來進行研究。由電氣生理學胞內與胞外記錄法所得到的結果中發現,第一型單純疱疹病毒感染後可以成功地在海馬迴組織切片中誘發出癲癇放電的體外模式。第一型單純疱疹病毒感染後對於海馬迴CA3區域的興奮性神經訊息傳遞並未產生明顯的影響,而是會改變CA3神經元本身細胞膜的特性及興奮度,包括靜止膜電位產生去極化、細胞膜阻抗增加以及後過極化振幅下降。除此之外,GABAB所媒介的抑制性神經傳遞作用也會受到抑制。除以電氣生理學確認第一型單純疱疹病毒造成癲癇發作之機制外,我們也利用免疫組織化學法、結晶紫染色法與Timm氏染色法分別確認第一型單純疱疹病毒在切片組織上之分佈情形、感染後會使細胞型態之變化情形及苔狀纖維重新分佈生長的現象。另一方面,我們也發現在第一型單純疱疹病毒感染七天後,無法以電氣生理學紀錄法記錄到神經元的活性表現。此現象可能與第一型單純疱疹病毒不斷大量複製並毒殺神經元所致,因此採用抗病毒藥物acyclovir 20 mM來前處理抑制病毒進行複製。結果發現,所記錄到的細胞活性會趨向於穩定狀態且也能夠記錄到感染七天的神經元活性表現。另外以蘇木素-伊紅染色法也確認第一型單純疱疹病毒感染後會使神經元受損。從電氣生理學以及組織病理學的結果可以知道在腦組織切片培養系統中感染第一型單純疱疹病毒後,會藉由改變細胞膜本身的興奮性與GABAB抑制作用造成神經元過度興奮而誘發癲癇的發作;另外,其複製過量也會對神經元造成不可逆地傷害而導致神經元的死亡。
英文摘要
(Abstract in English)

Epilepsy is a chronic disorder characterized by recurrent self-limited seizures with excessive discharges throughout localized or generalized groups of neurons in the brain. Recurrent seizures, if frequent, interfere with the patients’ ability to perform day-to-day activities; however, judicious use of antiepileptic medications allows about 65-70% of epileptic patients to be seizure-free. It means that about 25-30% of epileptic patients can’t be cured by classical antiepileptic drugs. This type of drug-resistant epilepsy is called “intractable epilepsy”. However, the consequences and the underlying mechanisms of the generation of intractable epilepsy remain unclear. Recently, clinical observations have described the detection of herpes simplex virus (HSV) in the brain in patients who presented with intractable seizures. It is therefore hypothesized that seizure activity in a subset of epilepsy cases is caused by persistent HSV infection in the seizure foci. To elucidate the role of HSV infection in the development of chronic seizure disorders and the possible epileptogenic mechanisms, we have developed an in vitro organotypic slice culture model of epileptic seizures induced by persistent HSV type 1 (HSV-1) infection and use electrophysiological recordings and immunohitochemistry techniques. Intracellular and extracellular recordings revealed that HSV-1 infection may successfully induce epileptiform discharge pattern on the slice culture in the CA3 region. The postinfected CA3 pyramidal cells exhibited a more depolarizing resting membrane potential concomitanted with an increase in the membrane input resistance, and had an reduction in the amplitude of afterhyperpolarization amplitude and a marked decrease in the GABAB-mediated inhibition. In contrast, the excitatory synaptic transmission in the hippocampal CA3 region did not significantly change. Besides electrophysiological recordings, we also checked HSV-1 distribution, neuron morphological change, and mossy fiber sprouting on cultured slices using immunohistochemistry, Nissl stain, and Timm stain respectively. Accidently, we found that the hippocampal CA3 neurons didn’t present neuronal activities after 7 days HSV-1 infection. We suggested that it may be due to the global neuronal death after chronic HSV-1 infection. In final set of experiment, we cultured the slices in the presence of acyclovir (20 mM) to inhibit HSV-1 replication and found that most CA3 neurons recorded by intracellular recording tended to present stable phenotype. These findings confirmed the hypothesis that HSV-1 continuous replication may cause cell damage. This hypothesis was also confirmed by hematoxylin-eosin staining method. Judging from the characteristics of the electrophysiological correlates, and neuropathology, this chronic slice model has points of resemblance with recent interpretation of the HSV hypothesis for limbic seizures that caused from change of neuron membrane properties and decreased GABAB inhibitory effect, and it may be used to investigate the pathogenesis and therapeutic strategies of human pharmacoresistant epilepsy. Furthermore, HSV-1 infection may injure neurons and eventually lead to neuronal death.
目 錄
頁碼
中文摘要 4-6
英文摘要 7-9
縮寫檢索表 10-13
緒論 14-55
材料與方法 56-70
病毒株與細胞株 57
病毒計量 57-59
組織切片培養 59
感染病毒 60
電氣生理學紀錄法 60-63
抗病毒藥物acyclovir對神經元活性表現的影響 63-64
組織切片染色法 64-68
統計方法 68
藥品購得 68-70
結果 71-88
討論 89-101
圖表 102-140
參考文獻 141-160
自述 161
參考文獻
(References)

王聖予、李麗俐、吳秀玲、周啟馥、楊志元與陳建和,最新醫用微生物學(上) (下),藝軒圖書出版社,1999。

吳柏林,醫用微生物學(下冊),藝軒圖書出版社,1992。

Acosta, E. P., and Fletcher, C. V. (1997). Valacyclovir. The Annals of Pharmacotherapy 31: 185-191.

Amaral, D. G., and Witter, M. P. (1995). The rat nervous system, Academic Press, Inc..

Anderson, N. E., Powell, K. F., and Croxson, M. C. (1993). A polymerase chain reaction assay of cerebrospinal fluid in patients with suspected herpes simplex encephalitis. Journal of Neurology Neurosurgery and Psychiatry 56: 520-525.

Aubert, M., O’toole, J., and Blaho, J. A. (1999). Induction and prevention of apoptosis in human HEp-2 cells by herpes simplex virus type 1. Journal of Virology 73: 10359-10370.

Aubert, M., and Blaho, J. A. (2001). Modulation of apoptosis during herpes simplex virus infection in human cells. Microbes and Infection 3: 859-866.

Babb, T. L., Pretorius, J. K., Kupfer, W. R., and Crandall, P. H. (1989). Glutamate decarboxylase-immunoreactive neurons are preserved in human epileptic hippocampus. Journal of Neuroscience 9: 2562-2574.

Baker, D. E., and Roizman, B. (1992). The unique sequence of the herpes simplex virus I L component contains an additional translated open reading frame designated UL49.5. Journal of Virology 66: 562-566.

Balish, M. J., Abrams, M. E., Pumfery, A. M., and Brandt, C. R. (1992). Enhanced inhibition of herpes simplex virus type 1 growth in human corneal fibroblasts by combinations of interferon-alpha and -gamma. Journal of Infectious Diseases 166: 1401-1403.

Barnett, B. C., Dolan, A., Telford, E. A. R., Davison, A. J., and McGeoch, D. J. (1992). A novel herpes simplex virus gene (UL49A) encodes a putative membrane protein with counterparts in other herpesviruses. Journal of General Virology 73: 2167-2171.

Beck, C., Moulard, B., Steinlein, O., Guipponi, M., Vallee, L., Montpied, P., Baldy-Moulnier, M., and Malafosse, A. (1994). A nonsense mutation in the alpha4 subunit of the nicotinic acetylcholine receptor (CHRNA4) cosegregates with 20q-linked benign neonatal familial convulsions (EBNI)
Neurobiology of Disease 1: 95-99.

Bourgeois, M., Vinikoff, L., Lellouch-Tubiana, A., and Sainte-Rose, C. (1999). Reactivation of herpes virus after surgery for epilepsy in a pediatric patient with mesial temporal lobe sclerosis: case report. Neurosurgery 44: 633-636.

Brody, T. M., Larner J., and Minneman, K. P. (1998). Human pharmacology: molecular to clinical, Mosby-Year Book, Inc..

Brooks-Kayal, A. R., Shumate, M. D., Jin, H., Rikhter, T. Y., and Coulter, D. A. (1998). Selective changes in single cell GABAA receptor subunit expression and function in temporal lobe epilepsy. Nature Medicine 4: 1166-1172.

Buckmaster, P. S., and Dudek, F. E. (1997). Network properties of the dentate gyrus in epileptic rats with hilar neuron loss and granule cell axon reorganization. Journal of Neurophysiology 77: 2685-2696.

Buckmaster, P. S., and Dudek, F. E. (1999). In vivo intracellular analysis of granule cell axon reorganization in epileptic rats. Journal of Neurophysiology 81: 712-721.

Buckmaster, P. S., Jongen-Relo, A. L., Davari, S. B., Wong, E. H. (2000). Testing the disinhibition hypothesis of epileptogenesis in vivo and during spontaneous seizures. Journal of Neuroscience 20: 6232-6240.

Buhl, E. H., Otis, T. S., and Mody, I. (1996). Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy model. Science 271: 369-373.

Cantin, E. M., Hinton, D. R., Chen, J., and Openshaw, H. (1995). Gamma interferon expression during acute and latent nervous system infection by herpes simplex virus type 1. Journal of Virology 69: 4898-4905.

Carson, M. J., Reilly, C. R., Sutcliffe, J. G., and Lo, D. (1998). Mature microglia resemble immature antigen-presenting cells. GLIA 22: 72-85.

Cavalheiro, E. A., Santos, N. F., and Priel, M. R. (1996). The pilocarpine model of epilepsy in mice. Epilepsia 37: 1015-1019.

Cohen, G. H., Ponce de Leon, M., Diggelmann, H., Lawrence, W. C. Vernon, S. K., and Eisenberg, R. J. (1980). Structural and analysis of the capsid polypeptides of herpes simplex virus types 1 and 2. Journal of Virology 34: 521-531.

Colgin, M. A., Smith, R. L., and Wilcox, C. L. (2001). Inducible cyclic AMP early repressor produces reactivation of latent herpes simplex virus type 1 in neurons in vitro. Journal of Virology 75: 2912-2920.

Coltman, B. W., Earley, E. M., Shahar, A., Dudek, F. E., and Ide, C. F. (1995). Factors influencing mossy fiber collateral sprouting in organotypic slice cultures of neonatal mouse hippocampus. Journal of Comparative Neurology 362: 209-222.

Davenport, C. J., Brown, W. J., and Babb, T. L. (1990). Sprouting of GABAergic and mossy fiber axons in dentate gyrus following intrahippocampal kainate in the rat. Experimental Neurology 109: 180-190.

Deatly, A. M., Spivack, J. G., Lavi, E., and Fraser, N. (1987). RNA from an immediate-early region of the type 1 herpes simplex virus genome is present in the trigeminal ganglia of latently infected mice. Proceedings of the National Academy of Sciences of the United States of America 84: 3204-3208.

De Lanerolle, N. C., Kim, J. H., Robbins, R. J., and Spencer, D. D. (1989). Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy. Brain Research 32: 387-395.

De Lorey, T. M., Handforth, A., Anagnostaras, S. G., Homanics, G. E., Minassian, B. A., Asatourian, A., Fanselow, M. S., Delgado-Escueta, A., Ellison, G. D., and Olsen, R. W. (1998). Mice lacking the beta3 subunit of the GABAA receptor have the epilepsy phenotype and many of the behavioral characteristics of Angelman syndrome. Journal of Neuroscience 18: 8505-8514.

De Stasio, P. R., and Taylor, M. W. (1989). Trans-activation of herpes simplex virus type 1 immediate early genes is specifically inhibited by human recombinant interferons. Biochem. Biophys. Res. Commun. 159: 439-444.

Dingledine, R., McBain, C. J., and McNamara, J. O. (1990). Excitatory amino acid receptors in epilepsy. TiPS 11: 334-338.

Duprat, F., Lesage, F., Fink, M., Reyes, R., Heurteaux, C., and Lazdunski, M. (1997). TASK, a human background K+ channel to sense external pH variations near physiological pH. The EMBO Journal 16: 5464-5471.

During, M. J., Ryder, K. M., and Spencer, D. D. (1995). Hippocampal GABA transporter function in temporal-lobe epilepsy. Nature 376: 174-177.

Durner, M., Sander, T., Greenberg, D. A., Johnson, K., Beck-Mannagetta, G., and Janz, D. (1991). Localization of idiopathic generalized epilepsy on chromosome 6p in families of juvenile myoclonic epilepsy patients. Neurology 41: 1651-1655.

Eisenstein, B. I. (1990). The polymerase chain reaction. A new method of using molecular genetics for medical diagnosis. New England Journal of Medicine 322: 178-183.

Elmslie, F. V., Rees, M., Williamson, M. P., Kerr, M., Kjeldsen, M. J., Pang, K. A., Sundqvist, A., Friis, M. L., Chadwick, D., Richens, A., Covanis, A., Santos, M., Arzimanoglou, A., Panayiotopoulos, C. P., Curtis, D., Whitehouse. W. P., Gardiner, R. M. (1997). Genetic mapping of a major susceptibility locus for juvenile myoclonic epilepsy on chromosome 15q. Human Molecular Genetics 6: 1329-1334.

Emmert, D. H. (2000). Treatment of common cutaneous herpes simplex virus infections. American Family Physician 61: 1697-1703.

Ernst, M. E., and Franey, R. J. (1998). Acyclovir- and ganciclovir- induced neurotoxicity. The Annals of Pharmacotherapy 32: 111-113.

Farrell, M. J., Dobson, A. T., and Feldman, L. T. (1991). Herpes simplex virus latency-associatedtranscript is a stable intron. Proceedings of the National Academy of Sciences of the United States of America 88: 790-794.

Feduchi, E., Alonso, M., and Carrasco, L. (1989). Human gamma interferon and tumor necrosis factor exert a synergistic blockade on the replication of herpes simplex virus. Journal of Virology 63: 1354-1359.

Field, H. J. (2001). Herpes simplex virus antiviral drug resistance-current trrends and future prospects. Journal of Clinical Virology 21: 261-269.

Fink, M., Lesage, F., Duprat, F., Heurteaux, C., Reyes, R., Fosset, M., and Lazdunski, M. (1998). A neuronal two P domain K+ channel stimulated by arachidonic acid and polyunsaturated fatty acids. The EMBO Journal 17: 3297-3308.

Fisher, R.S., and Coyle, J. T. (1991). Neurotransmitters and epilepsy, A John Wiley & Sons, Inc..

Flemington, E. K. (2001). Herpesvirus lytic replication and the cell cycle: arresting new developments. Journal of Virology 75: 4475-4481.

Flügel, A., Bradl, M., Kreutzberg, G. W., and Graeber, M. B. (2001). Transformation of donor-derived bone marrow precursors into host microglia during autoimmune CNS inflammation and during the retrograde response to axotomy. Journal of Neuroscience Research 66: 74-82.

Gambardella, A., Annesi, G., De Fusco, M., Patrignani, A., Aguglia, U., Annesi, F., Pasqua, A. A,, Spadafora, P., Oliveri, R. L., Valentino, P., Zappia, M., Ballabio, A., Casari, G., and Quattrone, A. (2000). A new locus for autosomal dominant nocturnal frontal lobe epilepsy maps to chromosome 1. Neurology 55: 1467-1471.

Gaudreau, A., Hill, E., Balfour, H. H. Jr., Erice, A., and Boivin, G. (1998). Phenotypic and genotypic characterization of acyclovir-resistant herpes simplex viruses from immunocompromised patients. Journal of Infectious Diseases 178: 297-303.

Geiger, K. D., Howes, E. L., and Sarvetnick, N. (1994). Ectopic expression of gamma interferon in the eye protects transgenic mice from intraocular herpes simplex virus type 1 infections. Journal of Virology 68: 5556-5567.

Geiger, K. D., Gurushanthaiah, D., Howes, E. L., Lewanndowski, G. A., Reed, J. C., Bloom, F. E., and Sarvetnick, N. E. (1995). Cytokine-mediated survival from lethal herpes simplex virus infection: role of programmed neuronal death. Proceedings of the National Academy of Sciences of the United States of America 92: 3411-3415.

Geiger, K. D., Nash, T. C., Sawyer, S., Krahl, T., Patstone, G., Reed, J. C., Krajewski, S., Dalton, D., Buchmeier, M. J., and Sarvetnick, N. (1997). Interferon-gamma protects against herpes simplex virus type 1-mediated neuronal death. Virology 238: 189-197.

Gibson, W., and Roizman, B. (1972). Proteins specified y herpes simplex virus. VIII. Characterization and composition of multiple capsid forms of subtypes 1 and 2. Journal of Virology 10: 1044-1057.

Gilbert, M. E. (1988). Formamidine pesticides enhance susceptibility to kindled seizures in amygdala and hippocampus of the rat. Neurotoxicology and Teratology 10: 221-227.

Gilman, A. G., Goodman, L. S., Rall, T. W., and Murad, F. (1985). Goodman and Gilman’s the pharmacological basis of therapeutics, MacMillan Publishing Company.

Graziosi, C., Pantaleo, G., Gantt, K. R., Fortin, J. P., Demarest, J. F., Cohen, O. J., and Sekaly, P. (1994). Lack of evidence for the dichotomy of Th1 and Th2 predominance in HIV-infected individuals. Science 265: 248-252.

Griffith, J. F., and Ch’ien, L. T. (1983). Herpes simplex virus encephalitis. Medical Clinics of North America 67: 991-1008.

Grose, C., and Wiedeman, J. (1997). Generic acyclovir vs. famciclovir and valacyclovir. Pediatric Infectious Diseases 16: 838-841.

Guffond, T., Dewilde, A., Lobert, P. E., Caparros-Lefebvre, D., Hober, D., Wattre, P. (1994). Significance and clinical relevance of the detection of herpes simplex virus DNA by the polymerase chain reaction in cerebrospinal fluid from patients with presumed encephalitis. Clinical Infectious Diseases 18: 744-749.

Haarr, L., and Skulstad, S. (1994). The herpes simplex virus type 1 particle: structure and molecular functions. APMIS 102: 321-346.

Hablitz, J. J., and Johnson, D. (1981). Endogenous nature of spontaneous bursting in hippocampal pyramidal neurons. Cell Molecular Neurobiology 1: 325-333.

Halford, W. P., Gebhardt, B. M., and Carr, D. J. J. (1997). Acyclovir blocks cytokine gene expression in trigeminal ganglia latently infected with herpes simplex virus type 1. Virology 238: 53-63.

Hallmann, K., Durner, M., Sander, T., and Steinlein, O. K. (2000). Mutation analysis of the inwardly rectifying K(+) channels KCNJ6 (GIRK2) and KCNJ3 (GIRK1) in juvenile myoclonic epilepsy. American Journal of Medical Genetics 96: 8-11.

Heinemann, U., Gabriel, S., Jauch, R., Schulze, K., Kivi, A., Eilers, A., Kovacs, R., and Lehmann, T. N. (2000). Alterations of glial cell function in temporal lobe epilepsy. Epilepsia 41 Suppl. 6: s185-s189.

Hille, B. (1992). G protein-coupled mechanisms and nervous signaling. Neuron 9: 187-195.

Hosford, D. A., Crain, B. J., and Cao, Z. (1991). IncreasedAMPA-sensitive quisqualate receptor binding and reduced NMDA receptor binding in epileptic human hippocampus. Journal of Neuroscience 11: 428-434.

Houser, C. R. (1990). Granular cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy. Brain Research 535: 195-204.

Irmiere, A. F., Manos, M. M., Jacobson, J. G., Gibbs, J. S., and Coen, D. M. (1989). Effect of an amber mutation in the herpes simplex virus thymidine kinase gene on polypeptide synthesis and stability. Virology 168: 210-220.

Jacobs, R. F. (1998). Neonatal herpes simplex virus infections. Seminars in Perinatology 22: 64-71.

Jan, L. Y., and Jan, Y. N. (1989). Voltage-sensitive ion channels. Cell 56: 13-25.

Janjua, N. A., Itano, T., Kugoh, T., Hosokawa, K., Nakano, M., Matsui, H., and Hatase, O. (1992). Familial increase in plasma glutamic acid in epilepsy. Epilepsy Research 11: 37-44.

Janjua, N. A., Kabuto, H., and Mori, A. (1992). Increased plasma glutamic acid in a genetic model of epilepsy. Neurochemistryl Research 17: 293-296.

Jay, V., Becker, L. E., Otsubo, H., Cortez, M., Hwang, P., Hoffman, H. J., and Zielenska, M. (1995). Chronic encephalitis and epilepsy (Rasmussen’s encephalitis): detection of cytomegalovirus and herpes simplex virus 1 by the polymerase chain reaction and in situ hybridization. Neurology 45: 108-117.

Jay, V., Hwang, P., Hoffman, H. J., Becker, L. E., and Zielenska, M. (1998). Intractable seizure disorder associated with chronic herpes infection. HSV1 detection in tissue by the polymerase chain reaction. Child’s Nerve System 14: 15-20.

Jin, W., Sugaya, A., Tsuda, T., Ohguchi, H., and Sugaya, E. (2000). Relationship between large conductance calcium-activated potassium channel and bursting activity. Brain Research 860: 21-28.

Kandel, E. R., Schwartz, J. H., and Jessell, T. M. (2000). Principles of neuroscience, McGraw-Hill Press.

Keller, P. M., Fyfe, J. A., Beauchamp, L., Lubbers, C. M., Furman, P. A., Schaeffer, H. J., Elion, G. B. (1981). Enzymatic phosphorylation of acyclic nucleoside analogs and correlations with antiherpetic activities. Biochemical Pharmacology 30: 3071-3077.

Kim, Y., Bang, H., and Kim, D. (2000). TASK-3, a new memberof the tandem pore K+ channel family. The Journal of Biological Chemistry 275: 9340-9347.

Knowles W. D., Awad, I. A., and Nayel, M. h. (1992). Differences of in vitro electrophysiology of hippocampal neurons from epileptic patients with mesiotemporal sclerosis versus structural sclerosis. Epilepsia 33: 601-609.

Koprowski, H., Zheng, Y. M., Heber-Katz, E., Fraser, N., Rorke, L., Fu, Z. F., Hanlon, C., and Dietzschold, B. (1993). In vivo expression of inducible nitric oxide synthase in experimentally induced neurologic diseases. Proceedings of the National Academy of Sciences of the United States of America 90: 3024-3027.

Kosz-Vnenchak, M., Jacobson, J., Coen, D. M., and Knipe, D. M. (1993). Evidence for a novel regulatory pathway for herpes simplex virus gene expression in trigeminal ganglion neurons. Journal of Virology 67: 5383-5393.

Kramer, M. F., and Coen, D. M. (1995). Quantification of transcripts from the ICP4 and thymidine kinase genes in mouse ganglia infected with herpes simplex virus. Journal of Virology 69: 1389-1399.

Kreutzberg, G. W. (1996). Microglia: a sensor for pathological events in the CNS. Trends in Neurosciences 19: 312-318.

Lauritzen, I., Blondeau, N., Heurteaux, C., Widmann, C., Romey, g., and Lazdunski, M. (2000). Polyunsaturated fatty acids are potent neuroprotectors. The EMBO Journal 19: 1784-1793.

Legendre, P., and Westbrook, G. L. (1991). Noncompetitive inhibition of gamma-aminobutyric acidA channels by Zn. Molecular Pharmacology 39: 267-274.

Lehesjoki, A. E., Koskiniemi, M., Pandolfo, M., Antonelli, A., Kyllerman, M., Wahlstrom, J., Nergardh, A., Burmeister, M., Sistonen, P., and Norio, R. (1992). Linkage studies in progressive myoclonus epilepsy: Unverricht-Lundborg and Lafora's diseases. Neurology 42: 1545-1550.

Leonoudakis, D., Gray, A. T., Winegar, B. D., Kindler, C. H., Harada, M., Taylor, D. M., Chavez, R. A., Forsayeth, J. R., and Yost, C. S. (1998). An open rectifier potassium channel with two pore domains in tandem cloned from rat cerebellum. Journal od Neuroscience 18: 868-877.

Lesage, F., Guillemare, E., Fink, M., Duprat, F., Lazdunski, M., Romey, G., and Barhanin, J. (1996). TWIK-1, a ubiquitous human weakly inward rectifying K+ channel with a novel structure. The EMBO Journal 15: 1004-1011.

Lewis, T. B., Leach, R. J., Ward, K., O'Connell, P., and Ryan, S. G. (1993). Genetic heterogeneity in benign familial neonatal convulsions: identification of a new locus on chromosome 8q. American Journal of Human Genetics 53: 670-675.

Liu, A. W., Delgado-Escueta, A. V., Serratosa, J. M., Alonso, M. E., Medina, M. T., Gee, M. N., Cordova, S., Zhao, H. Z., Spellman, J. M., and Peek, J. R. (1995). Juvenile myoclonic epilepsy locus in chromosome 6p21.2-p11: linkage to convulsions and electroencephalography trait. American Journal of Human Genetics 57: 368-381.

Liu, T., Tang, Q., and Hendricks, R. L. (1996). Inflammatory infiltration of the trigeminal ganglion after herpes simplex virus type 1 corneal infection. Journal of Virology 70: 264-271.

MacVicar, B. A., and Dudek, F. E. (1981). Electrotonic coupling between pyramidal cells: a direct demonstration in rat hippocampal slices. Science 213: 782-785.

Maggi, E., Mazzetti, M., Ravina, A., Annuniato, F., De Carli, M., Piccinni, M. P., Manetti, R., Carbonari, M., Pesce, A. M., Del Prete, G., and Romagnani, S. (1994). Ability of HIV to promote a TH1 to TH0 shift and to replicate preferentially in TH2 and TH0 cells. Science 265: 244-248.

Margerison, J. H., and Corsellis, J. A. N. (1966). Epilepsy and the temporal lobes. Brain 89: 699-710.

Martin, R. E., Henken, D. B., and Hill, J. M. (1996). Altered expression and changing distribution of nerve growth associated protein GAP-43 during ocular HSV-1 infection in the rabbit. Journal of Neurovirology 2: 127-135.

Mathern, G. W., Babb, T. L., Pretorius, J. K., and Leite, J. P. (1995). Reactive synaptogenesis and neuron densities for neuropeptide Y, somatostatin, and glutamate decarboxylase immunoreactivity in the epileptogenic human fascia dentata. Journal of Neuroscience 15: 3990-4004.

Mayer, M. L., and Miller, R. J. (1990). Excitatory amino acid receptors, second messengers and regulation of intracellular Ca2+ in mammalian neurons. TiPS 11: 254-260.

McCormick, D. A., and Contreras, D. (2001). On the cellular and network bases of epileptic seizures. Annual Review of Physiology 63: 815-846.

McDonald, J. W., Garofalo, E. A., and Hood, T. (1991). Altered excitatory and inhiitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy. Annals of Neurology 29: 529-541.

McGeoch, D. J., Delrymle, M. A., Davison, A. J., Dolan, A., Frame, M. C., McNab, D., Perry, L. J., Scott, J. E., and Taylor, P. (1988). The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. Journal of General Virology 69: 1531-1574.

McGrath, N., Anderson, N. E., Croxson, M. C., and Powell, K. F. (1997). Herpes simplex encephalitis treated with acyclovir: diagnosis and long term outcome. Journal of Neurology, Neurosurgery, and Psychiatry 63: 321-326.

McKernan, R. M., and Whiting, P. J. (1996). Which GABAA-receptor subtypes really occur in the brain?. Trends in Neurosciences 19: 139-143.

Meneton, P., Lesage, F., and Barhanin, J. (1999). Potassium ATPases, channels, and transporters: an overview. Seminars in Nephrology 19: 438-457.

Meldrum, B. S. (1992). Excitatory amino acids in epilepsy and potential novel therapies. Epilepsy Research 12: 189-196.

Meyding-Lamade, U., Haas, J., Lamade, W., Stingele, K., Kehm R., Fath A., Heinrich, K., Hagenlocher, B. S., and Wildemann, B. (1998). Herpes simplex virus encephalitis: long-term comparative study of viral load and the expression of immunologic nitric oxide synthase in mouse brain tissue. Neuroscience Letters 244: 9-12.

Nalder, J. V., Perry, B. W., abd Cotman, C. W. (1980). Selective reinnervation of hippocampal area CA1 and the fascia dentata after destruction of CA3-CA4 afferents with kainic acid. Brain Research 182: 1-9.

Nicholls, J. G., Martin, A. R., and Wallace, B. G. (1992). From neuron to brain: a cellular and molecular approach to the function of the nervous system, Sinaner Associates, Inc..

Nicoll, R. A., Malenka, R. C., and Kauer, J. A. (1990). Functional comparison of neurotransmitter receptor subtypes in mammalian central nervous system. Physiology Review 70: 513-565.

North, R. A. (1989). Twelfth Gaddum memorial lecture. Drug receptors and the inhibition of nerve cells. British Journal of pharmacology 98: 13-28.

Obenaus, A., Esclapez, M., and Houser, C. R. (1993). Loss of glutamate decarboxylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures. Journal of Neuroscience 13: 4470-4485.

Olsen, R. W., Wamsley, J. K., McCabe, R. T., Lee, R. J., and Lomax, P. (1985). Benzodiazepine/gamma-aminobutyric acid receptor deficit in the midbrain of the seizure-susceptible gerbil. Proceedings of the National Academy of Sciences of the United States of America 82: 6701-6705.

Overall J. C. (1994). Herpes simplex virus infection of the fetus and newborn. Pediatric Annals. 23: 131-136.

Perry, V. H., Andersson, P., and Gordon, S. (1993). Macrophages and inflammation in the central nervous system. Trends in Neurosciences 16: 268-273.

Peterson, G. M., Ribak, C. E., and Oertel, W. H. (1985). A regional increase in the number of hippocampal GABAergic neurons and terminals in the seizure-sensitive gerbil. Brain Reseach 340: 384-389.

Peterson, G. M., and Ribak, C. E. (1987). Hippocampus of the seizure-sensitive gerbil is a specific site for anatomical changes in the GABAergic system. Journal of Comparative Neurology 261: 405-422.

Phillips, H. A., Scheffer, I. E., Berkovic, S. F., Hollway, G. E., Sutherland, G. R., and Mulley, J. C. (1995). Localization of a gene for autosomal dominant nocturnal frontal lobe epilepsy to chromosome 20q 13.2. Nature Genetics 10: 117-118.

Phillips, H. A., Scheffer, I. E., Crossland, K. M., Bhatia, K. P., Fish, D. R., Marsden, C. D., Howell, S. J., Stephenson, J. B., Tolmie, J., Plazzi, G., Eeg-Olofsson, O., Singh, R., Lopes-Cendes, I., Andermann, E., Andermann, F., Berkovic, S, F., and Mulley, J. C. (1998). Autosomal dominant nocturnal frontal-lobe epilepsy: genetic heterogeneity and evidence for a second locus at 15q24. American Journal of Human Genetics 63: 1108-1116.

Piredda, S., and Gale, K. (1985). A crucial epileptogenic site in the deep prepiriform cortex. Nature 317: 623-625.

Poza, J. J., Saenz, A., Martinez-Gil, A., Cheron, N., Cobo, A. M., Urtasun, M., Marti-Masso, J. F., Grid, D., Beckmann, J. S., Prud'homme, J.F., Lopez de Munain, A. (1999). Autosomal dominant lateral temporal epilepsy: clinical and genetic study of a large Basque pedigree linked to chromosome 10q. Annals of Neurology 45: 182-188.

Puchhammer-Stöckl, E., Heinz, F. X., Kundi, M., Popow-Kraupp, T., Grimm, G., Millner, M. M., and Kunz, C. (1993). Evaluation of the polymerase chain reaction for diagnosis of herpes simplex virus encephalitis. Journal of Clinical Microbiology 31: 146-148.

Rixon, F. J., Cross, A. M., Addison, C., and Preston, V. G. (1988). The products of herpes simplex virus gene UL26 which are involved in DNA packaging are strongly associated with empty but not with full capsids. Journal of General Virology 69: 2879-2891.

Routbort, M. J., Bausch, S. B., and McNamara, J. O. (1999). Seizures, cell death, and mossy fiber sprouting in kainic acid-treated organotypic hippocampal cultures. Neuroscience 94: 755-765.

Sah, P. (1996). Ca2+-activated K+ currents in neurones: types, physiological roles and modulation. Trends in Neurosciences 19: 150-154.

Sanker, S., Chandrasekharan, U. M., Wilk, D., Glynias, M. J., Karnik, S. S., and Husain, A. (1997). Distinct multisite synergistic interactions determine substrate specificities of human chymase and rat chymase-1 for angiotensin II formation and degradation. Journal of Biological Chemistry 272: 2963-2968.

Sasadeusz, J. J., Tufaro, F., Safrin, S., Schubert, K., Hubinette, M. M., Cheung, P. K., and Sacks, S. L. (1997). Homopolymer mutational hot spots mediate herpes simplex virus resistance to acyclovir. Journal of Virology 71: 3872-3878.

Sawtell, N. M., Thompson, R. L., Stanberry, L. R., and Bernstein, D. I. (2001). Early intervention with high-dose acyclovir treatment during primary herpes simplex virus infection reduces latency and subsequent reactivation in the nervous system in vivo. Journal of Infectious Diseases 184: 964-971.

Schlitt, M., Bucher, A. P., Stroop, W. G., Pindak, F., Bastian, F. O., Jennings, R. A., Lakeman, A. D., and Whitley, R. J. (1988). Neurovirulence in an experimental focal herpes encephalitis: relationship to observed seizures. Brain Research 440: 293-298.

Schmutzhard, E. (2001). Viral infections of the CNS with special emphasis on herpes simplex infections. Journal of Neurology 248: 469-477.

Schröder, W., Hinterkeuser, S., Seifert, G., Schramm, J., jabs, R., Wilkin, G. P., and Steinhäuser, C. (2000). Functional and molecular properties of human astrocytes in acute hippocampal slices obtained from patients with temporal lobe epilepsy. Epilepsia 41 Suppl. 6: s181-s184.

Schwartzkroin, P. A., and Prince, D. A. (1976). Microphysiology of human cerebral cortex studied in vitro. Brain Research 115: 497-500.

Schwartzkroin, P. A., and Haglund, M. M. (1986). Spotaneous rhythmic synchronous activity in epileptic human and normal monkey temporal lobe. Epilepsia 27: 523-533.

Selmaj, K., Brosnan, C. F., and Raine, C. S. (1992). Expression of heat shock protein-65 by oligodendrocytes in vivo and in vitro: implications for multiple sclerosis. Neurology 42: 795-800.

Shepherd, G. M. (1998). The synaptic organization of the brain, Oxford University Press.

Slesinger, P. A., Stoffel, M., Jan, Y. N., and Jan, L. Y. (1997). Defective g-aminoutyric acid type B receptor-activated inwardly rectifying K+ currents in cerebellar granule cells isolated from weaver and Girk2 null mutant mice. Proceedings of the National Academy of Sciences of the United States of America 94: 12210-12217.

Smart, T. G. (1992). A novel modulatory binding site for zinc on the GABAA receptor complex in cultured rat neurones. Journal of Physiology 447: 587-625.

Smith, J. G., Raper, S. E., Wheeldon, E. B., Hackney, D., Judy, K., Wilson, J. M., and Eck, S. L. (1997). Intracranial administration of adenovirus expressing HSV-TK in combination with ganciclovir produces a dose-dependent, self-limiting inflammatory response. Hum. Gene. Ther. 8: 943-954.

Smith, R. L., Morroni, J., and Wilcox, C. L. (2001). Lack of effect of treatment with penciclovir or acyclovir on the establishment of latent HSV-1 in primary sensory neurons in culture. Antiviral Research 52: 19-24.

Snow, R. W., and Dudek, F. E. (1984). Synchronous epileptiform bursts without chemical transmission in CA2, CA3 and dentate areas of the hippocampus. Brain Research 298: 382-385.

Steinhäuser, C., Schröder, W., Hinterkeuser, S., Seifert, G., and Schramm, J. (1998). Functional analysis of astrocytes in acute hippocampal slices derived from patients with temporal lobe epilepsies. Social Neuroscience Abstract 24: 278.

Stevens, J. G. (1989). Human herpesviruses: a consideration of the latent state. Microbilogical Reviews 53: 318-332.

Studahl, M., Rosengren L., Gunter G., and Hagber L. (2000). Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction. Journal of Neurology 247: 636-642.

Swanson, T. H. (1995). The patophysiology of human mesial temporal lobe epilepsy. Journal of Clinical Neurophysiology 12: 2-22.

Tauck, D. L., and Nalder, J. V. (1985). Evidence of functional mossy fiber sprouting in hippocampal formation of kainic aid-treated rats. Journal of Neuroscience 5: 1016-1022.

Taylor, S., Drake, S., and Pillay, D. (1999). Genital herpes, "the new paradigm". Journal of Clinical Pathology 52: 1-4.

Templeton, N. S. (1992). The polymerase chain reaction. History, methods, and applications. Diagnostic Molecular Pathology 1: 58-72.

Thackray, A. M., and Field, H. J. (2000). The effects of antiviral therapy on the distribution of herpes simplex virus type 1 to ganglionic neurons and its consequences during, immediately following and several months after treatment. Journal of General Virology 81: 2385-2396.

Traub, R.D., and Wong, R.K. (1982). Cellular mechanism of neuronal synchronization in epilepsy. Science 216: 745-747.

Trevathan, E. (2002). Infantile spasms and Lennox-Gastaut syndrome. Journal of Children Neurology 17 suppl. 2: 2s9-2s22.

Tyring, S. K., Douglas, J. M., Corey, L., Spruance, S. L., and Esmann, J. (1998). A randomized, placebo-controlled comparison of oral valacyclovir and acyclovir in immuno-competent patients with recurrent genital herpes infections. Archives of Dermetology 134: 185-191.

Ustacelebi, S. (2001). Diagnosis of herpes simplex virus infections. Journal of Clinical Virology 21: 255-259.

Valyi-Nagy, T., Olson, S. J., Valyi-Nagy, K., Montine T. J., and Dermody, T. S. (2000). Herpes simplex virus type 1 latency in the murine nervous system is associated eith oxidative damage to neurons. Virology 278: 309-321.

Van Gelder, N. M., Janjua, N. A., Metrakos, K., MacGibbon, B., and Metrakos, J. D. (1980). Plasma amino acids in 3/sec spike-wave epilepsy. Neurochemistry Research 5: 659-671.

Wagner, E. K., Devi-Rao, G., Feldman, L. T., Dobson, A. T., Zhang, Y. F., Flanagan, W. M., and Stevens, J. G. (1988). Physical characterization of the herpes simplex virus latency-associated transcript in neurons. Journal of Virology 62: 1194-1202.

Walev, I., Dienes, H. P., Bohl, J., Podlech, J., and Falke, D. (1995). Correlation of virus replication, cytokine (TNF-alpha and IL-1) producing cells, neuronal necrosis and inflammation after intranasal infection of mice with herpes simplex virus strains of different virulence. Archives of Virology 140: 1957-1967.

Ward, P. L., and Roizman, B. (1994). Herpes simplex genes: the blueprint of a successful human pathogen. Trends in Genetics 10: 267-274.

Watanabe, Y., Johnson, R. S., Butler, L. S., Binder, D. K., Spiegelman, B. M., Papaioannou, V. E., and McNamara, J. O. (1996). Null mutation of c-fos impairs structural and functional plasticities in the kindling model of epilepsy. Journal of Neuroscience 16: 3827-3836.

Weissbecker, K. A., Durner, M., Janz, D., Scaramelli, A., Sparkes, R. S., Spence, M. A. (1991). Confirmation of linkage between juvenile myoclonic epilepsy locus and the HLA region of chromosome 6. American Journal of Medical Genetics 38: 32-36.

Wheless, J. W., and Constantinou, J. E. C. (1997). Lennox-Gastaut syndrome. Pediatric Neurology 17: 203-211.

Whitley, R., and Roizman, B. (2001). Herpes simplex virus infections. The Lancet 357: 1513-1518.

Wong, R. K., Traub, R. D. (1983). Synchronized burst discharge in disinhibited hippocampal slice. I. Initiation in CA2-CA3 region. Journal of Neurophysiology 49: 442-458.

Young, B., and Heath, J. W. (2000). Wheater’s functional histology: a text and colour atlas, Churchill Livingstone.
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
系統版面圖檔 系統版面圖檔