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研究生: 黃聖洋
Huang, Sheng-Yang
論文名稱: 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
Prolong electrophysiological and neurobehavioral efficacy of melatonin in a stroke model in rats
指導教授: 李宜堅
Lee, E-Jian
張冠諒
Chang, Guan-Liang
學位類別: 碩士
Master
系所名稱: 工學院 - 醫學工程研究所
Institute of Biomedical Engineering
論文出版年: 2007
畢業學年度: 95
語文別: 中文
論文頁數: 73
中文關鍵詞: 褪黑激素電生理神經保護缺血性腦中風
外文關鍵詞: neurogenesis, melatonin, electrophysiological recovery, neuroplasticity, Neuroprotection, ischemic neuronal damage, stroke
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  • 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。

    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.

    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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