2016-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/645174摘要：腦室出血（intraventricularhemorrhage）是一種臨床神經重症疾病，常造成嚴重的後遺症或死亡。腦室內的出血可能藉由擠壓腦組織、神經毒性反應、水腦症、與血管痙攣等機轉，導致腦部的損傷。腦部血管痙攣（cerebralvasospasm）是顱內蜘蛛膜下腔出血後常見的一種反應，但這種情況在腦室出血後的臨床表現與病理機轉尚缺乏有系統的研究，仍待進一步釐清。在蜘蛛膜下腔出血的病患，血塊分解後的產物會誘發腦部血管的收縮；腦室內的出血，血塊分解後的物質會順著腦脊髓液循環流到蜘蛛膜下腔，很可能也透過類似的機轉引起血管收縮反應，但發生率、嚴重程度、位置、出現時間、與病人預後可能不盡相同。因此，本計畫旨在針對腦室出血後的腦血管痙攣情形，進行臨床研究與致病機轉探討。在臨床研究部分，將招募腦室出血合併水腦症的病患，記錄臨床參數與影像檢查資料，並進行積極治療（早期腦室引流與腦室內血塊溶解，與後續腰椎引流），同時抽取腦室腦脊髓液與腰椎腦脊髓液，分析其中與血管痙攣及發炎相關之生物標記的變化，以及統計與病患預後的相關性。在實驗研究方面，我們將使用腦室出血的大鼠動物模式，以雷射都普勒測量腦部微血流變化，與免疫組織反應分析血管組塞程度與細胞凋亡情形；另外將血管痙攣相關分子highmobilitygroupbox1(HMGB1)的誘餌受器solubleisformsofreceptorforadvancedglycationendproducts(sRAGE)注射至腦脊髓液內，檢驗是否有抑制血管痙攣的效果。另外將腦室出血大鼠的腦脊髓液，加入體外培養的神經細胞與血管內皮細胞，分析發炎與細胞凋亡等訊息傳遞路徑的活化情形。本項研究成果將提供腦室出血的重要資訊，包括積極清除腦室出血對患者預後的影響、阻斷HMGB1分子在腦室出血動物的療效、與血管痙攣及發炎相關的生物標記變化。這些資訊將有助於創新腦室出血的治療方式，進而改善病患的預後。<br> Abstract: Intraventricular hemorrhage (IVH), bleeding in the cerebral ventricular system, is adevastating neurological disease that carries high morbidity and mortality. IVH can lead to braindamage by several mechanisms: mass effect, neurotoxicity, hydrocephalus, and vasospasm.Cerebral vasospasm is a well-recognized phenomenon after subarachnoid hemorrhage (SAH), yetits clinical significance and pathophysiology in the case of IVH are less studied and merit furtherinvestigation. In SAH, the blood degradation products in the CSF are capable of inducing cerebralvasoconstriction in the subarachnoid space; similar mechanisms might operate in IVH patients, yetthe incidence, severity, location, timing, and prognosis of vasospasm may be different. Thereforewe propose the current research project to carry out detail stuidies for IVH. Regarding clinicalinvestigation, all patients with moderate to severe IVH and concomitant hydrocephalus willundergo standard treatment with external ventricular drainage, and intraventricular fibrinolysis withUrokinase followed by lumbar CSF drainage. The CSF from ventricular drain and lumbar drain willbe sampled, and quantified for various molecules related to vasospasm and inflammation. Thepatient’s outcome will be correlated with the clinical parameters and level of biomarkers. Forlaboratory studies, we will use an animal model of rat IVH to monitor the surface cerebral bloodflow by laser Doppler video microscope, and measure vessel thrombosis and cell apoptosis byimmunohistochemistry. A decoy receptor, soluble isforms of receptor for advanced glycationendproducts (sRAGE), will be injected into the CSF circulation to block high mobility group box 1(HMGB1), a spasmogen, for prevention of vasospasm. We will also use neuronal and endothelialcell culture system to study the signaling transduction pathway of apoptosis and inflammationfollowing IVH. The aim of this project is to evaluate the efficacy of minimally invasive clearanceof ventricular clot by early intraventricular fibrinolysis therapy and subsequent lumbar drain in IVHpatients, and the novel therapeutic approach targeting the HMGB1 molecules in an IVH animalmodel. The chronological change of biomarkers related to vasospasm and inflammation will beelucidated as well. These results may serve for future design of optimal therapy against IVH.腦室出血血管痙攣腦室引流腦室內血塊溶解腰椎引流腦脊髓液血管痙攣物質HMGB1Srageintraventricular hemorrhagevasospasmventricular drainageintraventricular fibrinolysislumbar drainCSFspasmogenHMGB1sRAGE