体外血脑屏障细胞模型的建立

文章综述了体外血脑屏障细胞模型建立的基本方法，包括单层脑微血管内皮细胞分离与培养、胶质细胞与内皮细胞共培养和三维立体细胞模型，并对模型的要求及其意义进行阐述。     

脑微血管内皮细胞与周细胞共培养构建体外血脑屏障模型

目的 应用原代培养的大鼠脑微血管内皮细胞(brain microvascular endothelial cell,BMVEC)与脑周细胞共培养建立可模拟在体状态的稳定体外血脑屏障(blood-brain barrier,BBB)模型.方法 原代分离、纯化培养大鼠BMVEC和周细胞,通过免疫细胞化学染色方法鉴定分离的细...     

体外血脑屏障细胞模型的建立

文章综述了体外血脑屏障细胞模型建立的基本方法,包括单层脑微血管内皮细胞分离与培养、胶质细胞与内皮细胞共培养和三维立体细胞模型,并对模型的要求及其意义进行了阐述。     

星形胶质细胞诱导维持血脑屏障特性

血脑屏障的结构、发生和诱导维持对神经系统的生理病理研究有重要意义。近年来对星形胶质细胞通过其分泌产物近距离参与对血脑屏障完整性的诱导维持的研究受到重视，对于指导临床实践具有重要作用。     

星形胶质细胞诱导维持血脑屏障特性

血脑屏障的结构、发生和诱导维持对这神经系统的生理病理研究有重要意义。近年来对星形胶质细胞通过其分泌产物近距离参与对血脑屏障完整性的诱导维持的研究受到重现，对于指导临床实践具有重要作用。     

周细胞在血脑屏障中的作用

周细胞是血脑屏障的一种重要细胞成分,在脑微血管生成、内皮细胞紧密连接形成、血脑屏障分化、微血管动态运动和结构稳定性方面起调节作用.周细胞在一些疾病,如脑血管病、神经退行性疾病、神经免疫性疾病和外伤性脑损伤中,呈现很独特的功能特性.文章对周细胞在血脑屏障中的作用做了综述.     

周细胞在血脑屏障中的作用

周细胞是血脑屏障的一种重要细胞成分,在脑微血管生成、内皮细胞紧密连接形成、血脑屏障分化、微血管动态运动和结构稳定性方面起调节作用.周细胞在一些疾病,如脑血管病、神经退行性疾病、神经免疫性疾病和外伤性脑损伤中,呈现很独特的功能特性.文章对周细胞在血脑屏障中的作用做了综述.     

血脑屏障结构研究近况

血脑屏障是维持中枢神经系统内环境稳定的结构基础。文章综述了内皮细胞，ＥＣ紧密连接，星形胶质细胞以及基膜等方面的细胞生物学分子生物学若干进展，并分析了其临床意义。     

血脑屏障结构研究近况

血脑屏障(BBB)是维持中枢神经系统(CNS)内环境稳定的结构基础。文章综述了内皮细胞(EC)、EC紧密连接(TJs)星形胶质细胞以及基膜(BM)等方面的细胞生物学及分子生物学若干进展,并分析了其临床意义。     

加强血脑屏障的通透性有助于清除狂犬病毒感染

据Medscape．com2007年9月12日报道（原载J Virol 2007；81：7993—7998），最新研究发现，通过小鼠试验证明加强血脑屏障（BBB）的通透性能够使免疫效应因子渗入从而避免致死性狂犬病毒的感染。[第一段]     

大鼠局灶性脑缺血后血脑屏障葡萄糖转运蛋白1表达的变化

目的研究局灶性脑缺血后血脑屏障葡萄糖转运蛋白1(GLUT1)表达的变化。方法采用线栓法制作大鼠大脑中动脉闭塞模型,用免疫组化方法观察脑缺血后1小时、3小时、6小时、12小时、1天、2天、3天、7天时血脑屏障GLUTl表达的动态变化。结果脑缺血后3小时血脑屏障GLUT1的表达开始增加．以后逐渐升高,1天时达高峰,2天时下降．7天时与假手术组比较无显著差异。结论脑缺血后血脑屏障GLUT1的表达增加;此对缺血脑组织具有保护作用。     

一氧化碳与肝硬化大鼠血脑屏障通透性的关系

目的 研究肝硬化大鼠血浆一氧化碳（ＣＯ）水平与血脑屏障通透性改变之间的关系。方法 将ＳＤ大鼠分为两组，ＣＣｌ４肝硬化模型组（ｎ＝１０）及正常对照组（ｎ＝１０），用联二亚硫酸盐还原法测定血浆ＣＯ的含量，用伊文思蓝法测定血脑屏障通透性，生理多导仪测定血压、心率等。结果 与对照组相比，肝硬化组血浆ＣＯ水平明显升高［（１８．３７±１．７９）μｍｏｌ／Ｌ ｖｓ （１０．２７±１．２１）μｍｏｌ／Ｌ，ｔ＝７．５，Ｐ＜０．０１］而平均动脉压（ｋＰａ）降低（１８．９３±０．７１　ｖｓ　１５．９２±０．７４），ｔ＝５．８３，Ｐ＜０．０１；血脑屏障通透性增加，脑内伊文思蓝含量肝硬化组明显高于对照组（１８．５２±１．３９ ｖｓ１５．０８±１．０６）ｎｇ／ｍｇ，ｔ＝３．９４，Ｐ＜０．０１。在肝硬化组血浆 ＣＯ水平与脑内伊文思蓝含量成正相关（ｒ＝０．７２，Ｐ ＜ ０．０１）而与平均动脉压成负相关（ｒ＝－０．６７，Ｐ＜０．０５）。结论 ＣＯ作为一种信使分子，不仅参与肝硬化大鼠低血压的发生，还与血脑屏障通透性增加有关，可能是肝硬化易诱发肝性脑病的重要介质之一。     

RANTES在急性胰腺炎血-脑脊液屏障通透性变化中的作用

目的 观察急性胰腺炎(AP)大鼠脑组织正常T细胞表达与分泌的活化调节因子(regulated on activation,normal T-cell expressed and secreted,RANTES)和occludin在大脑中的表达,探讨RANTES表达与血-脑脊液屏障通透性变化之间的关系.方法 将49只SD大鼠按数字表法随机分为假手术(SO)组,急性水肿性胰腺炎(AEP)3、6 h组和急性坏死性胰腺炎(ANP)3、6、12、24 h组.以0.5%和5%牛磺胆酸钠逆行胰胆管注射制备AEP和ANP模型.采用RT-PCR、Western blotting和免疫组化法检测脑组织RANTES和occludin的mRNA及蛋白的表达.结果 SO组,AEP 3、6组,ANP 3、6、12、24 h组RANTES mRNA表达量分别为0、0、0、0.36±0.05、0.47 4-0.04、0.65 4-0.05、0.83±0.07,蛋白表达量为0、0、0、0.42±0.03、0.57±0.04、0.78±0.08、1.05±0.08,ANP组较SO组和AEP组显著增加(P<0.01);occludin mRNA表达量为1.21±0.07、1.17±0.07、1.15±0.08、0.84±0.07、0.77±0.05、0.64±0.09、0.56±0.09,蛋白表达量为1.18±0.08、1.16±0.10、1.11±0.10、0.90±0.03、0.65±0.05、0.57±0.05、0.48±0.05,ANP组较s0组和AEP组显著下降(P<0.01).RANTES表达与胰腺组织病理损伤呈正相关(r=0.936,P<0.001);occludin表达与胰腺组织病理损伤呈负相关(r=-0.900,P<0.001);RANTES和occludin呈负相关(r=-0.943,P<0.001).结论 ANP时大鼠脑组织RNANTES 表达呈进行性增高,occludin表达呈进行性下降,RANTES通过下调occludin蛋白表达而改变血-脑脊液屏障通透性.     

菌-肠-脑轴与血脑屏障通透性的相关性研究进展

肠道内数量庞大的菌群对宿主的生理病理功能有着不可忽视的影响.研究显示肠道菌群能够通过合成和释放一些重要的神经递质及调节因子来影响中枢神经系统的功能,肠道菌群的紊乱与血脑屏障完整性降低有关.肠道菌群的稳态在预防与治疗神经退行性疾病中有重要意义.本文拟综述血脑屏障完整性与菌-肠-脑轴相关性的最新进展,为从肠道出发治疗神经系统疾病提供新的方向.     

Altered blood-brain barrier permeability in rats with prehepatic portal hypertension turns to normal when portal pressure is lowered

AIM: To study the blood-brain barrier integrity in prehe-patic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 d after ligation when portal pressure is spontaneously normalized. METHODS: Adult male Wistar rats were divided into four groups: GroupⅠ: Sham14d, sham operated; GroupⅡ: PH14d, portal vein stenosis; (both groups were used 14 days after surgery); GroupⅢ: Sham40d, Sham operated and GroupⅣ: PH40d Portal vein stenosis (GroupsⅡandⅣused 40 d after surgery). Plasma ammonia, plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded. RESULTS: Forty days after stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished. CONCLUSION: The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility, Hemo-dynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment.     

Altered blood-brain barrier permeability in rats with prehepatic portal hypertension turns to normal when portal pressure is lowered

AIM: To study the blood-brain barrier integrity in prehepatic portal hypertensive rats induced by partial portal vein ligation, at 14 and 40 d after ligation when portal pressure is spontaneously normalized.METHODS: Adult male Wistar rats were divided into four groups: Group I: Sham_14d , sham operated; Group II: PH_14d , portal vein stenosis; (both groups were used 14 days after surgery); Group III: Sham_40d, Sham operated and Group IV: PH_40d Portal vein stenosis (Groups II and IV used 40 d after surgery). Plasma ammonia, plasma and cerebrospinal fluid protein and liver enzymes concentrations were determined. Trypan and Evans blue dyes, systemically injected, were investigated in hippocampus to study blood-brain barrier integrity. Portal pressure was periodically recorded.RESULTS: Forty days after stricture, portal pressure was normalized, plasma ammonia was moderately high, and both dyes were absent in central nervous system parenchyma. All other parameters were reestablished. When portal pressure was normalized and ammonia level was lowered, but not normal, the altered integrity of blood-brain barrier becomes reestablished.CONCLUSION: The impairment of blood-brain barrier and subsequent normalization could be a mechanism involved in hepatic encephalopathy reversibility. Hemodynamic changes and ammonia could trigger blood-brain barrier alterations and its reestablishment.     

不同时间微创颅内血肿清除对血脑屏障功能及预后影响的研究

目的 探讨不同时间颅内血肿微创清除术对高血压脑出血患者血脑屏障指数(BBB)、血清髓鞘碱性蛋白(MBP)及预后日常生活能力评分(ADL)的影响. 方法观察时间≤3.0 h 30例,3.1～8.0 h 32例,8.1～24.0 h 28例,＞24.0 h 22 例,对照分析其BBB、MBP及ADL的变化.结果 ≤3.0 h、3.1～8.0 h微创血肿清除术组BBB和MBP[(6.57±0.69)×10 3和(3.12±0.40)μg/L、(7.37±1.29)×10 3和(3.25±0.60)μg/L]均明显低于8.1～24.0 h、＞24.0 h组[(12.02±1.51)×10-3和(4.60±0.48)μg/L、(14.68±2.07)×10-3和(5.88±0.64)μg/L,Q＞13.8,P＜0.05];≤3.0 h,3.1～8.0 h微创血肿清除术组[(2.60±1.07)分、(3.06±0.91)分]均明显高于8.1～24.0h、＞24.0 h组[(4.00±0.67)分、(3.68±1.32)分,Q＞3.1,P＜0.05]. 结论≤8.0 h实施微创血肿清除术可减轻高血压脑出血患者细胞毒性对血脑屏障的损伤,从而减轻脑水肿,提高患者的生存质量.

Abstract：

Objective To explore the effects of minimally invasive removal of intracranial hematoma on blood-brain barrier (BBB) index, serum myelin basic protein (MBP) and activity of daily living (ADL) in hypertensive patients with cerebral hemorrhage.Methods Through observing 30cases operated within 3.0 hours, 32 case operated between 3. 1-8. 0 hours, 28 cases operated between 8. 1 to 24.0 hours and 22 cases operated over 24 hours, the changes of BBB index, serum MBP and ADL were analyzed. Results The BBB index and serum MBP were significantly lower in patients operated within 8. 0 hours than in patients operated over 8. 1 hours [≤3.0 hours group:(6.57±0.69)×10-3 and (3. 12±0.40)μg/L;3. 1-8.0 hours group: (7. 37±1.29)×10-3 and (3.25±0.60)μg/L;8. 1-2.0 hours group: ( 12. 02± 1.51 ) × 10 3 and (4. 60±0. 48)μg/L;over 24.0 hours group: ( 14. 68±2.07)×10-3 and (5.88±0.64)μg/L,Q＞13.8,P＜0. 05]. And the ADL was lower in patients operated within 8. 0 hours than in patients operated over 8. 1 hours [≤3.0 hours group: (2. 60± 1.07)scores; 3.1-8.0 hours group: (3. 06±0. 91 )scores;8. 1-24.0 hours group: (4.00±0.67) scores;over 24.0 hours group:(3.68±1.32)scores,Q＞3. 1,P＜0.05].Conclusions The minimally invasive surgery of intracranial hematoma within 8.0 hours can mitigate the cytotoxicity-damaged BBB so as to lighten brain edema and improve the patients quality of life.     

Evidence for early blood-brain barrier breakdown in experimental thiamine deficiency in the mouse

In order to assess the involvement of blood-brain barrier (BBB) breakdown in the pathogenesis of thiamine deficiency encephalopathy, autologous albumin immunohistochemistry was performed in mice which were rendered thiamine-deficient by pyrithiamine, a BBB-permeant antagonist of thiamine. In the presymptomatic animals until day 8 of the treatment, histological lesions were not detected by H&E staining. However, localized staining of albumin was evident, suggesting an extravascular leakage of the endogenous intravascular protein. On day 10 of thiamine deficiency, when neurological signs appeared, both histological lesions and massive albumin extravasation were demonstrated in all the animals. The BBB breakdown was only occasionally observed in the brains of mice treated with oxythiamine, a BBB-impermeant antagonist or in control animals. These results suggest that BBB breakdown is not only a phenomenon secondary to tissue destruction, but it is more directly involved in the pathogenesis of thiamine deficiency encephalopathy.     

脑脉通对老龄大鼠脑缺血再灌注血-脑脊液屏障损伤的保护作用

目的研究脑脉通对老龄大鼠脑缺血再灌注（1／R）血-脑脊液屏障（BBB）损伤的保护作用。方法采用线栓法复制局灶性脑缺血模型，分为假手术组、模型组、脑脉通组、尼莫地平组，后3组又分为脑缺血（I）3h和I／R6、12、24h,3、6d时间点。观察脑组织含水量、病理变化、免疫球蛋白（IgG）表达。结果模型组脑组织含水量升高，IgG漏出增加，BBB通透性增加。脑脉通降低脑组织含水量（I／R24h、3d）、减少IgG漏出（I／R24h～6d）、降低BBB通透性。结论脑脉通改善I／R脑损伤作用显著，其机制可能与改善BBB通透性、降低脑水肿有关。