內(nèi)源性調(diào)節(jié)性T細胞在SAH后腦血管痙攣及腦損傷中的作用.ppt

內(nèi)源性調(diào)節(jié)性T細胞在SAH后腦血管痙攣及腦損傷中的作用,2019/7/16,研究的目的及意義,SAH后腦血管痙攣、炎癥反應及神經(jīng)功能預后的改善是 一個非常復雜的病理 、生理、臨床過程。雖然進行了大量研究， 為止其 發(fā)生機制仍未完全明了。研究小鼠體內(nèi)內(nèi)源性調(diào)節(jié)性T細 對SAH后腦血管痙攣、炎癥反應及神經(jīng)功能預后的改善仍 將是今后一個時期的熱點。隨著研究的逐漸深入，將 會對內(nèi)源性調(diào)節(jié)性T細胞移植SAH的臨床治療及神經(jīng)功能預后帶來 深遠的影響。,2019/7/16,國內(nèi)外相關(guān)文獻,The Kinetics of Lymphocyte Subsets and Macrophages in Subarachnoid Space After Subarachnoid Hemorrhage in Rats,it has been suggested that humoral immunity plays a role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, there has been no quantitative assay for cellular immunity. We studied the kinetics of immune cells in the subarachnoid space after subarachnoid hemorrhage in the rat.,2019/7/16,A serial response of immunoreactive cells, which resembles that of the chronic allergic reaction observed in autoimmune diseases or delayed-type hypersensitivity, exists in the subarachnoid space after subarachnoid hemorrhage. The present results suggest that the initial response in cellular immunity, which is followed by humoral immunity and eicosanoid reactions, plays a role in eliciting the development of cerebral vasospasm.,2019/7/16,蛛網(wǎng)膜下腔出血后腦血管痙攣 分子機制的研究進展,2019/7/16,與NO代謝無關(guān)的CVS,2019/7/16,Statin-Induced T-Lymphocyte Modulation and Neuroprotection Following Experimental Subarachnoid Hemorrhage,Statins in fl uence immune system activities through echanisms independent of their lipidlowering properties. T cells can be subdivided based on cytokine secretion patterns into two subsets: T-helper cells type 1 (Th1) and type 2 (Th2). Independent laboratory studies have shown statins to be potent inducers of a Th2 switch in immune cell response and be neuroprotective in severalmodels of central nervous system (CNS) disease. This study was the fi rst to evaluate the immune modulating effects of statins in subarachnoid hemorrhage (SAH).,2019/7/16,The present study elucidated the potential role of a Th2 immune switch in statin provided neuroprotection following SAH.,2019/7/16,Matrix metalloproteinase-9 concentration in the cerebral extracellular fluid of patients during the acute phase of aneurysmal subarachnoid hemorrhage,Elevated cerebral interstitial pro-MMP-9 relates to early brain injury in aSAH patients. A larger prospective study should be performed to confirm whether patients with prolonged elevation or a second peak of cerebral pro-MMP-9 would be more likely to develop DCI and to confirm whether MMP-9, a mediator of neurovascular injury, would be worth to consider as a predictor of vasospasm.,2019/7/16,Trehalose treatment suppresses inflammation,oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage,Subarachnoid hemorrhage (SAH) frequently results in several complications, including cerebral vasospasm, associated with high mortality. Although cerebral vasospasm is a major cause of brain damages after SAH, other factors such as inflammatory responses and oxidative stress also contribute to high mortality after SAH.Trehalose is a non-reducing disaccharide in which two glucose units are linked by ,-1,1-glycosidic bond, and has been shown to induce tolerance to a variety of stressors in numerous organisms. In the present study, we investigated the effect of trehalose on cerebral vasospasm, inflammatory responses, and oxidative stress induced by blood in vitro and in vivo.,2019/7/16,trehalose has suppressive effects on several pathological vents after SAH,including vasospasm, inflammatory responses, and lipid peroxidation. Trehalose may be a new therapeutic approach for treatment of complications after SAH.,2019/7/16,properties within the cerebrospinal fluid after subarachnoid hemorrhage in vivo and in vitro,To functionally characterize pro-inflammatory and vasoconstrictive properties of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage (SAH) in vivo and in vitro.,2019/7/16,We functionally characterized inflammatory and vasoactive properties of patients CSF after SAH in vivo and in vitro. This pro-inflammatory milieu in the subarachnoid space might play a pivotal role in the pathophysiology of early and delayed brain injury as well as vasospasm development following SAH.,2019/7/16,研究內(nèi)容,2019/7/16,每項研究內(nèi)容均分4組 1、Tregs刪除組 2、SAH模型組 3、假手術(shù)組 4、PBS腹腔注射組 體重、窩別、喂養(yǎng)方法相同的小鼠隨機分組每組1015只小鼠；每只小鼠編號后 按計算機隨機表分4組，雙盲（研究者、負責資料收集和分析的人員也不了解分組情況） 較好地避免了偏倚。,研究方法 實驗動物處理 1、Tregs刪除,2019/7/16,2、SAH模型制作,3、假手術(shù)：遇到 阻力即停止繼續(xù)插入，并迅速退出線栓 4、PBS腹腔注射：經(jīng)腹腔注射與0.25mg CD25特異性抗體等體積的PBS。,2019/7/16,一、內(nèi)源性調(diào)節(jié)性T細胞對蛛網(wǎng)膜下腔出血（SAH）后腦血管痙攣的檢測內(nèi)容,檢測內(nèi)容,2019/7/16,局部腦血流量（regional cerebral blood flow, rCBF）檢測： 顱骨開窗，在立體定向儀控制下，在SAH前及SAH后12小時內(nèi)（或6小時）用激光多普勒血流計動態(tài)測量動物頂葉皮層rCBF。,2019/7/16,基底動脈形態(tài)學檢測：,2019/7/16,循環(huán)內(nèi)皮細胞檢測： 于SAH后3天、2周取靜脈血標本，用因子相關(guān)抗原免疫熒光染色檢測循環(huán)內(nèi)皮細胞（circulating endothelial cell, CEC），以反映血管內(nèi)皮細胞的損傷。,2019/7/16,于SAH后3天、2周，取動物腦底Willis動脈環(huán)及其相連的動脈制備勻漿液 PCR、Western blot等檢測腦動脈勻漿液中一氧化氮合酶（nitric oxide synthase, NOS）mRNA和蛋白含量 硝酸酶還原法測定NO含量 放射免疫分析法測定cGMP含量,2019/7/16,二、內(nèi)源性調(diào)節(jié)性T細胞移植SAH后神經(jīng)功能預后的改善作用,2019/7/16,感覺評分,2019/7/16,運動評分,2019/7/16,認知功能障礙評估,數(shù)據(jù)表示為動物找到沉