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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張芳嘉(Fang-Chia Chang) | |
| dc.contributor.author | I-Feng Kao | en |
| dc.contributor.author | 高儀楓 | zh_TW |
| dc.date.accessioned | 2021-06-16T23:38:13Z | - |
| dc.date.available | 2013-07-27 | |
| dc.date.copyright | 2012-07-27 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-07-25 | |
| dc.identifier.citation | 1. Aggleton JP, Brown MW. (1999). Episodic memory, amnesia, and the hippocampal-anterior thalamic axis. Behav Brain Sci., 22(3), 425-444.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/65354 | - |
| dc.description.abstract | 癲癇，為一種可能發生在任何年齡且分布在世界各地之慢性神經疾病。現有治療癲癇策略包括抗癲癇藥、切除性手術和迷走神經電刺激法；儘管如此，仍有約三分之一的病患無法藉由這些方式得到良好的癲癇發作控制。此類難以控制之癲癇型態，又稱為頑性癲癇（refractory epilepsy）。近年來，學者提出，視丘前核之腦深層電刺激術（deep brain stimulation of anterior thalamic nucleus, ATN DBS）為治療頑性癲癇的可能方法。DBS有四個可調整參數，分別是刺激目標、刺激強度、刺激頻率與刺激時機。目前經過數國許可為癲癇治療的刺激目標，只有ATN。在刺激條件中，現有文獻已指出高頻率、高強度的雙側電刺激有較佳治療效果。但治療癲癇之最佳刺激條件尚未有定論。
刺激時機依照刺激方式，又可分為連續式或間斷式之開放性刺激（open-looped）與閉鎖式刺激（closed-looped stimulation）。閉鎖式刺激係指根據大腦發出的訊號線索，只在癲癇快要發作前才給予電刺激的方法。為了找出治療頑性癲癇之適當閉鎖式刺激條件，我們利用pilocarpine這種化合物誘發大鼠癲癇。Pilocarpine誘發之癲癇發作能模擬人顳葉型癲癇，又具有可預期發作時間之優點，適合用於閉鎖式電刺激參數之研究。 本研究以腦波作為判斷癲癇發作之主要依據，並搭配行為影像紀錄。實驗第一天先手術植入腦波圖記錄電極，並將電刺激電極植入左側視丘前核，將其固定在大鼠頭部，到第八天時以腹腔注射方式給予大鼠280-290 mg/kg pilocarpine以誘發癲癇發作。刺激流程為，在給藥前不同的時間點，開始連續ATN DBS，且電刺激設定條件為每個脈衝時間90 μs、強度50 μA，刺激頻率200 Hz。結果發現，給藥前60分鐘開始連續給予大鼠單側ATN DBS能成功抑制癲癇發作活性。抑制效果包括閾值增加，腦波和行為上發作時間延遲，而且發展為癲癇重積（status epilepticus）的大鼠數目減少。在腦組織切片中，僅有不等程度之植入傷害引起的發炎反應。總括上述，本研究顯示長時間高頻率、低電流之單側ATN DBS也能具有癲癇抑制效果，此刺激條件對於神經組織僅具輕微傷害性。 | zh_TW |
| dc.description.abstract | Epilepsy is a chronic neurological disease which affects people of all ages and distributes worldwide. Current strategy for treating epilepsy includes medication, resective surgery and vagus nerve stimulation. In spite of these treatments, there are about one third of epileptic patients who still suffer from uncontrollable seizures. Refractory epilepsy is another name for any type of epilepsy that is resistant to medication. Recently, deep brain stimulation of anterior thalamic nucleus (ATN DBS) has been proposed as a promising therapy for refractory epilepsy. There are four main questions for DBS: (1) How to stimulate the brain? (2) Where is the stimulation target? (3) What is the stimulation parameter? (4) When should one start to stimulate the brain? On one hand, the approved stimulation target for epilepsy is ATN only. On the other hand, the stimulation parameters seem to be a high frequency and a high current. For now, there is no optimal stimulation for DBS on epilepsy treatment so far.
The way to stimulate the brain could be continuous or intermittent and be open-looped or closed-looped. The closed-looped stimulation is starting the stimulation when the cue of seizure attack appears. In order to figure out the suitable stimulation paradigm for a closed-looped stimulation system, we use the pilocarpine-induced epileptic rat model. Advantages of pilocarpine-induced epilepsy are simulation of human temporal lobe epilepsy and a predictable seizure onset. In this study, electroencephalogram (EEG) was the primary tool for monitoring and identifying seizure. Video-recording was an additional tool. The experiment started on Day one: the rats received EEG electrode with or without DBS electrode implantation.The DBS electrode was introduced to the left anterior thalamic nucleus. On Day eight, all rats were intraperitoneally injected with 280-290 mg/kg pilocarpineto induce seizures. Stimulation began at different time points before pilocarpine administration. The stimulation parameters were 200 Hz, 50 μA and the pulse width 90 μs. Our results showed 60 minutes pre-stimulation successfully suppressed seizure activity. The effects of suppressionincluded an increased seizure threshold, a delayed electrographic and behavioral seizure onset, and a decreased number of rats developed seizure and status epilepticus. In the histopathological findings, only mild inflammation was noted around the implanted site. We conclude that with high stimulation frequency, low stimulation current and prolongedstimulation duration, unilateral ATN DBS could be able to suppress seizures without severe tissue damages. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T23:38:13Z (GMT). No. of bitstreams: 1 ntu-101-R99629011-1.pdf: 2234838 bytes, checksum: 908f390408218eb02eb530b81ad980a7 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 口試委員會審定書…………………………………………………………… i
誌謝……………………………………………………………………………………… ii 中文摘要…………………………………………………………………………… iii 英文摘要…………………………………………………………………………… v 第一章 緒論……………………………………………………………… 1 第一節 研究背景與動機………………………………………… 1 第二節 研究目的……………………………………………………… 6 第二章 文獻回顧與探討………………………………………… 7 第一節 癲癇與癲癇生成………………………………………… 7 2-1.1 癲癇的基本介紹………………………………………… 7 2-1.2 癲癇生成…………………………………………………… 10 第二節 腦深層電刺激術於癲癇的相關研究……… 16 2-2.1 DBS應用於癲癇的臨床結果…………………… 16 2-2.2 ATN DBS應用於癲癇的實驗動物結果… 21 第三節 大鼠ATN的解剖位置、連結和功能………… 26 第四節 癲癇動物模式的選擇……………………………… 28 第三章 材料與方法……………………………………………… 31 第一節 實驗動物…………………………………………………… 31 第二節 立體定位手術…………………………………………… 31 第三節 實驗用藥…………………………………………………… 33 第四節 電刺激器與參數之設定………………………… 34 第五節 腦波圖－影像之記錄與分析………………… 34 第六節 實驗流程…………………………………………………… 35 第七節 腦組織採樣與檢查………………………………… 36 第八節 統計方法…………………………………………………… 37 第四章 結果…………………………………………………………… 38 第一節 Pilocarpine的效果……………………… 38 第二節 單側ATN DBS的效果………………………… 39 第三節 神經病理變化……………………………………… 41 第五章 討論…………………………………………………………… 43 第六章 結論…………………………………………………………… 52 第七章 圖表…………………………………………………………… 53 參考文獻………………………………………………………………………… 65 附錄………………………………………………………………………………… 78 | |
| dc.language.iso | zh-TW | |
| dc.subject | 癲癇 | zh_TW |
| dc.subject | 腦深層電刺激術 | zh_TW |
| dc.subject | 視丘前核 | zh_TW |
| dc.subject | 顳葉型癲癇大鼠模式 | zh_TW |
| dc.subject | pilocarpine | zh_TW |
| dc.subject | pilocarpine | en |
| dc.subject | anterior thalamic nucleus (ATN) | en |
| dc.subject | rat model of temporal lobe epilepsy | en |
| dc.subject | epilepsy | en |
| dc.subject | deep brain stimulation (DBS) | en |
| dc.title | 以大鼠顳葉型癲癇模式探討腦深層電刺激術於癲癇治療之作用 | zh_TW |
| dc.title | Effect of Deep Brain Stimulation for Epilepsy in the Rat Model of Temporal Lobe Epilepsy | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蔡崇豪,徐崇堯,李立仁,周碩彬 | |
| dc.subject.keyword | 癲癇,腦深層電刺激術,視丘前核,顳葉型癲癇大鼠模式,pilocarpine, | zh_TW |
| dc.subject.keyword | epilepsy,deep brain stimulation (DBS),anterior thalamic nucleus (ATN),rat model of temporal lobe epilepsy,pilocarpine, | en |
| dc.relation.page | 90 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-07-26 | |
| dc.contributor.author-college | 獸醫專業學院 | zh_TW |
| dc.contributor.author-dept | 獸醫學研究所 | zh_TW |
| 顯示於系所單位： | 獸醫學系 | |
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