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研究生: 陳睿生
Chen, Jui-Sheng
論文名稱: 腦中風後增加腦血障壁之通透性以促進細胞治療效果之研究
Enhancing the permeability of the brain blood barrier for promoting cell therapy efficacy in cerebral infarction
指導教授: 蔡坤哲
Tsai, Kuen-Jer
謝清河
Hsieh, C.H. Patrick
學位類別: 碩士
Master
系所名稱: 醫學院 - 臨床醫學研究所碩士在職專班
Institute of Clinical Medicine(on the job class)
論文出版年: 2014
畢業學年度: 102
語文別: 英文
論文頁數: 47
中文關鍵詞: 腦中風間葉幹細胞血腦障壁
外文關鍵詞: cerebral infarction, mesenchymal stem cell, blood brain barrier
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  • 中風,又稱為腦血管病變,是因為腦部血流供應失調造成的急性腦部功能受損。在現代的統計中一直是致死率相當高的疾病之一。
    間葉幹細胞(mesenchymal stem cells, MSCs)是一群具有多功能的幹細胞,它顯現類似纖維母細胞樣的外觀,並且在體外具有相當強的活性,可以分化成骨骼、軟骨、以及脂肪細胞。在先前的研究中,間葉幹細胞被證實會在受傷的腦組織中形成內生性的保護機制,促進神經以及血管的生成。
    我們利用大鼠中腦動脈阻塞的手術建立阻塞-再灌流後的大腦阻塞性中風的動物模式。首先,我們發現在中風急性期給予血管內皮生長因子(vascular endothelial growth factor, VEGF)能夠增加病灶處之血腦障壁通透性。其次,依先前的實驗發現,我們確認在中風急性期給予血管內皮生長因子能促進間葉幹細胞在中風處的滯留。藉由以上的治療,我們能夠進一步增加間葉幹細胞的治療效果並縮小中風後腦梗塞壞死的範圍。我們的研究證實在腦中風的情況下增加腦血管障壁的通透性可以促進間葉幹細胞的治療效果。

    A stroke, also called cerebrovascular accident (CVA), is the rapid loss of brain function due to disturbance in the blood supply to the brain. It is one of the major lethal diseases in the modern era.
    Mesenchymal stem cells (MSCs) are a heterogeneous population of cells that have fibroblast-like morphology, form colonies in vitro and can differentiate into bone, cartilage and fat cells. In previous studies, MSCs have been shown to activate endogenous restorative responses after brain injury, possibly by the enhancement of angiogenesis, neurogenesis and synaptogenesis.
    Here, a rat middle cerebral artery occlusion (MCAO) procedure was used to generate a stable ischemic-reperfusion model in the brain. First, we performed systemic pre-treatment with vascular endothelial growth factor (VEGF) to increase blood brain barrier (BBB) permeability, which showed that more large particles were recruited at acute stage post-stroke. Second, we successfully increased the MSCs retention in the infarcted area by early VEGF pretreatment post-stroke. Finally, the therapeutic effect of MSCs could be facilitated and the infarct size post-stroke could be minimized. These results suggest that enhancing the BBB permeability may promote cell therapy efficacy in cerebral infarction.

    Chapter 1. Introduction ------------------------------- 1 1.1 Introduction to stroke ------------------------ 1 1.2 Introduction to ischemic stroke and current treatment ---------------------- 2 1.3 Introduction to cell therapy ------------------ 4 1.4 Introduction to cell therapy for ischemic stroke 7 1.5 Introduction to vascular endothelial growth factor9 1.6 Introduction to blood brain barrier ----------- 9 1.7 Our previous observation and emphasis of hypothesis----------------------------------- 10 Chapter 2. Hypothesis --------------------------------- 12 Chapter 3. Specific Aims ------------------------------ 12 Chapter 4. Research Design and Methods ---------------- 13 Chapter 5. Results ------------------------------------ 18 5.1 Permeability of the blood–brain barrier ------- 18 5.2 Evaluation of cells retention ----------------- 19 5.3 Evaluation of treatment ----------------------- 19 Chapter 6. Discussion and Future Works ---------------- 21 6.1 Middle cerebral artery occlusion -------------- 21 6.2 To monitor and evaluate cell therapy ---------- 22 6.3 The VEGF level may affect the treatment of stroke in acute stage ------- 24 Chapter 7. Conclusion --------------------------------- 26 Tables and Figure Legends ----------------------------- 27 References -------------------------------------------- 34

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