2012-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/686865摘要：毛毛樣病是一種慢性進行性腦血管閉塞的疾病，因為顱內大血管閉塞，而導致小血管代償性擴張及亂長而形成異常的血管網。兒童的毛毛樣病以腦短暫缺血及癲癇等症狀居多，長期下來可能造成智力低下或認知功能異常等。這個疾病在病態生理上包含了血管阻塞與新生血管同時發生。病理上，這個過程與一些血管新生的生長因子相關，其他一些cytokines, cell adhesion molecules, vasculogenesis也有報告與毛毛樣病相關。正因為機制不明且影響預後的因子也相當欠缺，因此我們希望藉由腦脊髓液的研究來找到適合的生化指標；這樣的生化指標可以用來診斷疾病、預測疾病預後、監視疾病活性或評估治療效果等。第一部份我們將藉由先前已收集的毛毛樣病患童腦脊髓液進行cytokine-array的研究，研究結果將用來分析毛毛樣病的診斷與病態生理機轉。所得結果我們將與另三子計畫整合分析，看腦部灌流量化值、血管攝影定量值、患童認知功能及生化指標的關係。接下來再前瞻性的收集毛毛樣病人的腦脊髓液與血液，進行蛋白質體的研究。由於腦脊髓液內蛋白質含量很少，我們在此計畫利用－isobaric Tagging forRelative and Absolute Quantitation（簡稱iTRAQ），配合台灣大學基因體中心購置的質譜儀，進行1.腦脊髓液生化標記的尋找與確認、2.腦脊髓液對於血管內皮細胞angiogenesis functional assay 的研究、3.血中endothelial progenitor cell 與vasculogenesis相關性的研究。毛毛樣病患者的病程、嚴重度與造成的神經缺損將在其他子計畫中以各種臨床分析工具加以定量與評估，本計畫的研究結果將整合這些子計畫的結果，找出與MMD 臨床相關的生化指標。<br> Abstract: Moyamoya disease (MMD) is a chronic cerebrovascular disorder characterized byprogressive occlusion of bilateral internal carotid arteries (ICAs) with dilated collaterallenticulostriate and thalamoperforating arteries forming basal telangiectasia. Transientischemic attack and epilepsy is the main presenting symptoms of MMD in children. It mayalso cause cognitive impairment in long term. Pathologically, stenosis or occlusion of ICAshas been attributed to eccentric fibrocellular thickening of the intima following proliferationand necrosis of smooth muscle cells. These processes are reported to be associated withseveral cytokines and growth factors related to angiogenesis. An increasing number ofreports have been focusing on not only angiogenesis related to growth factors but alsovasculogenesis. Because the lack of understanding the pathophysiology of MMD, there is anurgent need to identify novel biomarkers which can be used to improve the diagnosis, predictthe disease progression, improve our understanding of the pathology or serve as therapeutictargets for neurodegenerative diseases like MMD.Because cerebrospinal fluid (CSF) is in direct contact with the central nervous system(CNS), it may reflect the biochemical state of the CNS under different physiological andpathological conditions and has been regarded as an excellent source for identifyingbiomarkers for neurological diseases. In the first part of this sub-project, we will study theCSF that has been collected during revascularization surgery in the past three years.Cytokine-array for the analysis of all related cytokines and growth factors and cell adhesionmolecules will be used to study the biochemical changes of the CSF in various stages oftreatment. The results will then be correlated with another three sub-projects which includethe quantitative analysis of angiographic blush, cerebral perfusion, and neuropsychologicalanalysis in MMD patients. We then prospectively collect CSF and blood from newdiagnosed patients with MMD. Due to the sparse of protein in CSF, we will use isobaricTagging for Relative and Absolute Quantitation (iTRAQ) for biomarkers identification andquantification of CSF. The angiogenesis functional assay of the CSF will also be studied.Identification and quantification of human endothelial progenitor cells from peripheral bloodsamples will be correlated with the angiogenesis and function outcome after surgery.The diagnosis, management, and studies of MMD involve various specialties. Thisintegrated study aims to combine the clinical, psychological, and basic science to set upand validate a study platform that may improve the outcome of MMD patients. It is hopedthat this study platform may be used in the study of various neurological disorders.