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崔冬雪 《军事医学科学院院刊》2012,36(9):718-720
随着人口老龄化的加剧,神经系统疾病的发生率越来越高,而血脑屏障成为治疗神经系统疾病过程的一道难题。血脑屏障既可以保护大脑不受外界有害物质的侵害,维持脑部内环境的稳定,同时也限制了药物进入脑部发挥其治疗作用。本文概述了目前已被证实能改善药物血脑屏障通透性的方法,如化学修饰,制剂改造,联合用药等,系统综述了有关提高药物血脑屏障透过率的思路及研究方法的进展。 相似文献
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N Grégoire 《Journal de radiologie》1990,71(8-9):481-487
The blood-brain barrier (BBB) is present on three sites: the brain vessels, the choroid plexus and the arachnoid membrane. It is made of nonfenestrated endothelial or epithelial cells interconnected by tight junctions. Biochemically, the BBB is formed by bimolecular layers of phospholipids into which globular proteins are inserted. Exchanges through the BBB depend on whether the substances exchanged are soluble in water or in lipids. Hydrosoluble substances are largely excluded from the brain by the BBB; liposoluble substances pass the barrier easily by passive or active mechanisms. Water movements through the BBB are related to variations in osmolality. These data are of the utmost importance in all brain diseases with rupture of the BBB and in all neuroradiological procedures using contrast media. 相似文献
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Mechanisms of blood-brain barrier breakdown 总被引:4,自引:0,他引:4
J. Greenwood 《Neuroradiology》1991,33(2):95-100
Summary The functional status of the blood-brain barrier (BBB) must be taken into account when designing and interpreting brain imaging techniques. The integrity of the BBB is affected in many diseases of the brain, with the potential involvement of a number of different but poorly understood cellular mechanisms. Factors known to disrupt the BBB experimentally include arachidonic acid and the eicosanoids, bradykinin, histamine and free radicals. These active compounds, released in pathological tissue, may alter cytosolic calcium levels and induce second messenger systems leading to an alteration in BBB permeability. Extravasation of plasma proteins may occurvia disrupted tight junctions, stimulation of fluid-phase vesicular transport or the formation of transcellular pores or channels. 相似文献
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目的 通过切开硬脑膜和蛛网膜与不切开硬脑膜的开颅手术分析大分子物质是否会进入脑脊液和脑实质内. 方法 将成年雄性SD大鼠采用随机数字表法分成3组,分别为实验组A、实验组B和对照组C.A组在全身麻醉下行开颅手术,剪开硬脑膜和蛛网膜;B组仅做硬脑膜外的开颅手术;C组只麻醉,不做开颅手术.使用伊文思蓝作为示踪剂来检测实验结果,分别于不同时间点(1,3,6,12,24,72 h、1周)之前0.5 h内通过静脉注射一定剂量的伊文思蓝,0.5 h后处死,收取脑标本.采用荧光分光光度计测量脑组织中伊文思蓝的含量,分别进行统计学处理.对照组除未做开颅手术外,其他处理同实验组.取一部分A组和B组大鼠分别于术前和术后3,72 h进行脑组织含水量测定. 结果 脑组织取材时可见A组1,3,6,12,24 h局部呈浅蓝色,72 h脑组织的浅蓝色较微弱,1周未发现蓝染.B组和C组局部脑组织未发现蓝染.A组术后1,3,6,12,24,72 h和1周脑组织中伊文思蓝的含量[(18.07±1.25)μg/ml、(36.21±0.78)μg/ml、(25.73±1.14)μg/ml、(16.53±0.84)μg/ml、(23.34±1.91)/μg/ml、(43.34±2.25)μg/ml、(25.27±1.88)μg/ml]均比B组[(3.15±0.45)μg/ml、(3.36±0.33)μg/ml、(2.98±0.54)μg/ml、(3.47±0.55)μg/ml、(3.54±0.37)μg/ml、(2.88±0.42)μg/ml、(2.85±0.22)μg/ml]和C组[(2.97±0.37)μg/ml]高(P<0.01).利用干湿重法进行术前、后脑组织含水量测定,结果显示术前后脑组织含水量改变差异无统计学意义(P>0.05). 结论 开颅术后一些大分子物质能通过头皮创面渗出,在硬脑膜缝合不十分严密的情况下,能越过血脑屏障和血脑脊液屏障直接进入蛛网膜下腔,并进入脑组织内. 相似文献
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目的 验证开颅手术前静脉注射美罗培南预防颅内感染的有效性.方法选择21~64岁的开颅手术患者,开颅手术前留置腰大池引流管,术前30min静脉给予美罗培南1.0g,给药的起始时间记为0点,采集静脉血和脑脊液标本时间为给药后0.5、1、2、3、4h,采用高效液相色谱法(HPLC)检测美罗培南浓度.结果血清峰浓度为(52.88±4.39)mg/L,达峰时间为30min.脑脊液峰浓度为(2.85±0.19)mg/L,达峰时间为2h.美罗培南术前静脉持续注射时脑脊液最大穿透率为13.75%±7.26%,最大穿透率出现的时间为静点后3h.结论 术前30min经静脉注射抗生素美罗培南,脑脊液中药物浓度在注射后2h达到最大值并可持续数小时.经静脉注射1.0g美罗培南,血清稳态药物浓度高于多数颅内感染常见致病菌的MIC90. 相似文献
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Summary Using two different models, the effect on the blood-brain barrier of intracarotid injections of sodium/meglumine ioxaglate at similar iodine concentrations (280mgI/ml) was investigated. In both models the degree of blood-brain barrier damage was assessed visually using Evans' Blue stain. Quantitative assessment of blood-brain barrier disruption was made by contrast enhancement as measured by CT of the dog brain, and by 99mTc-pertechnetate uptake by the brain in the rabbit model. No Evans' Blue staining was observed in any study using the canine/CT model. Slight staining was observed in two studies with ioxaglate using the rabbit/pertechnetate model. Statistical analysis of results from the canine/CT model did not detect any damage to the blood-brain barrier with either ioxaglate or saline control studies (P>0.1). However, in the rabbit/pertechnetate model a slight increase in disruption of the blood-brain barrier was observed with ioxaglate compared with control studies, but this was only significant at the 0.1 level. The results suggest that the rabbit/pertechnetate model is a more sensitive measure of blood-brain barrier disruption than the canine/CT model. This study also demonstrates that blood-brain barrier disruption following intracarotid injection of ioxaglate is minimal. 相似文献
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Muldoon LL Pagel MA Kroll RA Roman-Goldstein S Jones RS Neuwelt EA 《AJNR. American journal of neuroradiology》1999,20(2):217-222
BACKGROUND AND PURPOSE: Osmotic disruption of the blood-brain barrier (BBB) provides a method for transvascular delivery of therapeutic agents to the brain. The apparent global delivery of viral-sized iron oxide particles to the rat brain after BBB opening as seen on MR images was compared with the cellular and subcellular location and distribution of the particles. METHODS: Two dextran-coated superparamagnetic monocrystalline iron oxide nanoparticle contrast agents, MION and Feridex, were administered intraarterially in rats at 10 mg Fe/kg immediately after osmotic opening of the BBB with hyperosmolar mannitol. After 2 to 24 hours, iron distribution in the brain was evaluated first with MR imaging then by histochemical analysis and electron microscopy to assess perivascular and intracellular distribution. RESULTS: After BBB opening, MR images showed enhancement throughout the disrupted hemisphere for both Feridex and MION. Feridex histochemical staining was found in capillaries of the disrupted hemisphere. Electron microscopy showed that the Feridex particles passed the capillary endothelial cells but did not cross beyond the basement membrane. In contrast, after MION delivery, iron histochemistry was detected within cell bodies in the disrupted hemisphere, and the electron-dense MION core was detected intracellularly and extracellularly in the neuropil. CONCLUSION: MR images showing homogeneous delivery to the brain at the macroscopic level did not indicate delivery at the microscopic level. These data support the presence of a physiological barrier at the basal lamina, analogous to the podocyte in the kidney, distal to the anatomic (tight junction) BBB, which may limit the distribution of some proteins and viral particles after transvascular delivery to the brain. 相似文献
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C Chryssanthou T Palaia G Goldstein R Stenger 《Aviation, space, and environmental medicine》1987,58(11):1082-1086
Previous studies indicated that exposure to compression-decompression increases blood-brain barrier (BBB) permeability to vital dyes and antibiotics. This report concerns functional and ultrastructural BBB changes induced by altitude decompression. A 2% trypan blue solution was intravenously injected (4 ml.kg-1) into 29 experimental and 19 control rabbits. Some animals also received horseradish peroxidase. The experimental animals were subjected to 30,000 ft (4.3 psi) for 45 min. Controls were kept at ground level. The animals were sacrificed 90 min postinjection. Gross and microscopic examination and spectrophotometric dye determination revealed significantly greater tracer penetration in experimental brains (mean dye concentration 27.06 +/- 4.42 micrograms.g-1) than in controls (4.52 +/- 1.52 micrograms.g-1). No sex differences were noted. Electron microscopy suggested that the increased BBB permeability was due to transendothelial vesicular transport and, occasionally, to penetration through interendothelial junctions. These observations may have relevance to pharmacotherapy in space and at high altitudes and to the pathogenesis of altitude decompression sickness. 相似文献
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PURPOSE: To determine if focused ultrasound beams can be used to locally open the blood-brain barrier without damage to surrounding brain tissue and if magnetic resonance (MR) imaging can be used to monitor this procedure. MATERIALS AND METHODS: The brains of 18 rabbits were sonicated (pulsed sonication) in four to six locations, with temporal peak acoustic power ranging from 0.2 to 11.5 W. Prior to each sonication, a bolus of ultrasonographic (US) contrast agent was injected into the ear vein of the rabbit. A series of fast or spoiled gradient-echo MR images were obtained during the sonications to monitor the temperature elevation and potential tissue changes. Contrast material-enhanced MR images obtained minutes after sonications and repeated 1-48 hours later were used to depict blood-brain barrier opening. Whole brain histologic evaluation was performed. RESULTS: Opening of the blood-brain barrier was confirmed with detection of MR imaging contrast agent at the targeted locations. The lowest power levels used produced blood-brain barrier opening without damage to the surrounding neurons. Contrast enhancement correlated with the focal signal intensity changes in the magnitude fast spoiled gradient-echo MR images. CONCLUSION: The blood-brain barrier can be consistently opened with focused ultrasound exposures in the presence of a US contrast agent. MR imaging signal intensity changes may be useful in the detection of blood-brain barrier opening during sonication. 相似文献
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Modeling intracranial pressures in microgravity: the influence of the blood-brain barrier 总被引:1,自引:0,他引:1
INTRODUCTION: A majority of astronauts experience symptoms of headache, vomiting, nausea, lethargy, and gastric discomfort during the first few hours or days after entering a microgravity environment. Due to similarities in symptoms and their time evolution, it has been hypothesized that some of these conflicts are related to the development of benign intracranial hypertension in these individuals in microgravity. METHODS: This hypothesis was tested using a validated mathematical model that embeds the intracranial system in whole-body physiology. This model was used to predict steady-state intracranial pressures in response to various cardiovascular stimuli associated with microgravity, including changes in arterial pressure, central venous pressure, and blood colloid osmotic pressure. The model also allowed alterations of the blood-brain barrier due to factors such as gravitational unloading and increased exposure to radiation in space to be considered. RESULTS: Simulations predicted that intracranial pressure will increase significantly if, combined with a drop in blood colloid osmotic pressure, there is a reduction in the integrity of the blood-brain barrier in microgravity. DISCUSSION: These results suggest that in some otherwise healthy individuals microgravity environments may elevate intracranial pressure to levels associated with benign intracranial hypertension, producing symptoms that can adversely affect crew health and performance. 相似文献
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RATIONALE AND OBJECTIVES. The authors used magnetic resonance imaging (MRI) techniques to examine the effect of meningeal trauma produced by cisterna magna puncture on the integrity of the blood-cerebrospinal fluid barrier (BCB) in a rat model. METHODS. Intravenous gadolinium-DTPA (Gd-DTPA), a relaxation rate modifier which normally does not cross the BCB, was used as a probe to follow leakage of fluid across the BCB. After Gd-DTPA injection, cerebrospinal fluid (CSF) serial samples were obtained through the needle used to create the experimental trauma. These samples were subsequently examined in vitro by MRI to obtain their T1 relaxation rates and assayed by mass spectrometry for gadolinium and elemental iron concentrations. RESULTS. The iron levels reflected the severity of puncture-related subarachnoid hemorrhage. Rats with ongoing meningeal damage showed significantly higher CSF levels of gadolinium and significantly higher CSF T1 relaxation rates than controls at all samples times over 1 hour after the puncture. Blood in the CSF could not explain these changes because the CSF iron levels did not significantly differ from control levels. CONCLUSIONS. Intravenously administered Gd-DTPA can gain access to the subarachnoid space through minor defects in the BCB and cause significant increases in CSF T1 relaxation rates. 相似文献
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Intracarotid chemotherapy has been suggested as an additional mode of therapy in patients with brain tumors. Seven comatose patients received intracarotid 5-fluorouracil and adriamycin after intracarotid infusion of 25% mannitol to open the blood-brain barrier at the tumor site. Five of seven patients became fully functional for 3-12 months. Another 11 patients entered the study, of which nine are currently receiving therapy and are functional, and two have died, one from brain herniation. The results are encouraging and support the need for further research of this therapeutic method. 相似文献
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125I标记重组人β-神经生长因子在血脑屏障中通透性的研究 总被引:3,自引:2,他引:1
目的 研究β-神经生长因子(NGF)在血脑屏障中的通透 性。方法 将重组真核表达载体PcDNA3-β-NGF以脂质体转染COS-7细胞。将细胞培养上清经离子交换树脂层析进行分离纯化,观察纯化蛋白质对PC12细胞突起生长的作用,以^125I标记纯化蛋白南,Wistar大鼠尾静脉注射,以γ测量仪检测脑组织放射性。结果 PC12细胞培养结果示:纯化产物可促使其突起生长;注射后30min,脑组织放射性达高峰。结论 纯化的重组人β-NGF具有良好的生物学活性,且部分通透过高脑屏障。 相似文献
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F Iannotti C Fieschi B Alfano P Picozzi L Mansi C Pozzilli A Punzo G Del Vecchio G L Lenzi M Salvatore 《Journal of computer assisted tomography》1987,11(3):390-397
Blood-brain barrier (BBB) permeability to [68Ga]EDTA was measured by positron emission tomography (PET) in four normal volunteers and in 11 patients with brain tumors. A unidirectional transfer constant, Ki, was calculated applying multiple-time graphical analysis (MTGA). This method allows the detection of backflux from brain to blood and, by generalization, the measurement of the constant Kb (brain to blood). Furthermore, the need for an independent measurement of the intravascular tracer is obviated: MTGA itself provides an estimate of the cerebral plasma volume (Vp). In the four normal volunteers the Ki was 3.0 +/- 0.8 X 10(-4) ml g-1 min-1 (mean +/- SD) and the Vp 0.034 +/- 0.007 ml g-1. A net increase in Ki up to a maximum of 121.0 X 10(-4) ml g-1 min-1 (correspondent value of Kb = 0.025 min-1) as well as an increase of Vp was observed in malignant tumors. The input function was calculated using both the [68Ga]EDTA concentration in sequential arterial blood samples and, noninvasively, the activity derived from the superior sagittal sinus image. The values of Ki and Vp from these two calculations were in good agreement. The application of MTGA to PET permits the evaluation of passage of substances across the BBB without making assumptions about the compartments in which the tracer distributes. 相似文献
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目的:研究高功率微波辐射对大鼠血脑屏障结构和功能的影响。方法:以10、30和100mW/cm^2高功率微波源辐射66只二级雄性Wistar大鼠。于辐射后6h、1d、3d和7d灌注2%亚铁氰化钾和4.2%硫酸铁后取材,通过HE染色、组织化学、免疫组化和图像分析等技术,研究毛细血管形态、血脑屏障通透性及GFAP改变。结果:10mW/cm^2组大鼠血脑屏障无明显改变。30和100mW/cm^2组辐射后1~3d血管间隙增宽,组织水肿,指示剂通透性增加。上述改变于辐射后3d达高峰,7d基本恢复。皮质血管较海马血管改变明显,100mW/cm^2组重于30mW/cm^2组。30和100mW/cm^2组大鼠皮质和海马组织中GFAP表达增强,3d达高峰,7d仍高于假辐射组。结论:一定剂量高功率微波辐射可损伤大鼠血脑屏障结构和功能。 相似文献