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系統識別號 U0026-0812200913594023
論文名稱(中文) 缺血性腦中風大鼠模型使用褪黑激素於電生理與神經行為之效益
論文名稱(英文) Prolong electrophysiological and neurobehavioral efficacy of melatonin in a stroke model in rats
校院名稱 成功大學
系所名稱(中) 醫學工程研究所碩博士班
系所名稱(英) Institute of Biomedical Engineering
學年度 95
學期 2
出版年 96
研究生(中文) 黃聖洋
研究生(英文) Sheng-Yang Huang
電子信箱 p8694106@mail.ncku.edu.tw
學號 p8694106
學位類別 碩士
語文別 中文
論文頁數 73頁
口試委員 口試委員-鍾高基
口試委員-葉明龍
指導教授-李宜堅
指導教授-張冠諒
中文關鍵字 褪黑激素  電生理  神經保護  缺血性腦中風 
英文關鍵字 neurogenesis  melatonin  electrophysiological recovery  neuroplasticity  Neuroprotection  ischemic neuronal damage  stroke 
學科別分類
中文摘要 本研究旨在研究Melatonin對於大鼠缺血性腦中風之神經保護效益。近年來,Melatonin為神經科學之一熱門話題,相關研究發現Melatonin是一強而有效之自然抗氧化劑與自由基截取劑,是以有潛力降低缺血後的能量流失之神經保護劑。先前的研究已發現Melatonin於缺血性腦中風急性期有強而有效之神經保護效果。在本研究中,進一步探討褪黑激素於缺血性腦中風大鼠模型之急性期治療在電生理和神經行為上的回復,延長觀測時間以逐步追蹤Melatonin於急性期治療缺血性中風神經保護之效益,評估其進一步之神經保護特性與其神經保護潛能。利用大白鼠進行可逆轉之中大腦動脈縫線栓塞逐步研究探討缺血治療後之中長期追蹤,評估其進一步之神經保護特性與其神經保護潛能。並於可逆轉中大腦動脈縫線栓塞後7天,應用影像處理系統計算Nissl染色腦切片之栓塞大小並評估栓塞後個別神經運動感覺功能。由實驗結果發現,以5mg/kg之Melatonin進行靜脈注射為有效反應劑量,並於持續性中大腦動脈縫線栓塞後至少1.5小時仍有效神經保護作用。
總而言之,本研究觀察得到Melatonin是無毒性的並具有持續性的神經保護,故其對於神經外科手術的計畫性腦血管栓塞以及缺血性腦中風的病人具有潛在性的益處,值得進一步的研究。
英文摘要 The neuroprotective properties of melatonin, a strong natural antioxidant and free radical scavenger which decreases oxidative lipid peroxidation and DNA hydroxylation, and prevents against energy depletion during ischemia, will be evaluated in Sprague-Dawley rats subjected to 1-hour transient middle cerebral artery (MCA) occlusion. A experiments with delayed treatment of melatonin will be employed to examine whether it is neuroprotective following a long period of recovery using a model of reversible MCA occlusion. Postmortem infarct volumes will be determined by quantitative image analysis of Nissle-stained brain sections and by immunohistochemical methods. In addition, postischemic electrophysiological recovery, neurogenesis, synaptic arborization and axonal sprouting will be evaluated. The possible mechanisms of action relevant to long-term neuroprotective efficacy by which melatonin may exhibit the neuroprotective effects will also be evaluated in the model. The data will not only extend our original findings to the ischemic-reperfusion injury but also look at prolonged outcomes, thus, may provide a potential outlook to treat patients against ischemic stroke.
論文目次 中文摘要............................................Ⅰ
Abstract............................................Ⅱ
誌謝................................................Ⅲ
總目錄..............................................Ⅴ
圖目錄..............................................Ⅷ
表目錄..............................................Ⅹ
第一章 緒論
1-1腦血管疾病.......................................1
1-1-1腦血管循環的病理生理學.........................2
1-1-2腦血管意外(Cerebrovascular Accidents,CVA)...11
1-1-3臨床缺血性中風治療藥物........................14
1-2褪黑激素Melatonin...............................17
1-3電生理學的神經傳遞信號監測......................19
1-3-1動作電位傳導..................................19
1-3-2感覺神經病變..................................21
1-3-3體感覺誘發電位(Somatosensory Evoked Potential)22
1-4研究動機與目的..................................30
第二章 材料與方法
2-1實驗流程........................................32
2-2實驗方法........................................33
2-2-1動物準備和麻醉................................33
2-2-2體感覺誘發電位監測............................33
2-2-3大鼠中風模型-中大腦動脈阻塞手術(MCA occlusion)39
2-2-4 LCBF監測動物犧牲和量化缺血傷害...............41
2-2-5神經行為學檢查與體重測量......................42
2-2-6動物犧牲和切片染色............................46
2-2-7局部缺血傷害的量化............................48
2-3統計分析........................................49
第三章 結果
3-1生理參數之記錄..................................51
3-2核心體溫之監控..................................52
3-3局部腦皮質血流量之監測..........................52
3-4體感覺誘發電位記錄..............................55
3-5神經學檢查評估及體重減少量......................62
3-6大腦損害量化....................................63
第四章 討論
4-1體感覺誘發電位記錄..............................65
4-2神經行為評估.................................................67
4-3 Melatonin之神經保護效果........................68
第五章 結論與未來展望
5-1 結論與未來展望.................................69
參考文獻
自述
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