EFFECT OF INFLAMMATORY AGENTS ON ELECTRICAL-RESISTANCE ACROSS THE BLOOD-BRAIN-BARRIER IN PIAL MICROVESSELS OF ANESTHETIZED RATS
EFFECT OF INFLAMMATORY AGENTS ON ELECTRICAL-RESISTANCE ACROSS THE BLOOD-BRAIN-BARRIER IN PIAL MICROVESSELS OF ANESTHETIZED RATS
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DOI：
10.1016/0006-8993(95)00811-4
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发表时间：
1995-10-23
期刊：
影响因子：
2.9
通讯作者：
BUTT, AM
中科院分区：
文献类型：
--
作者：
BUTT, AM
用原位测量大鼠软脑膜微血管跨内皮细胞电阻的方法，观察了组胺、缓激肽和5-羟色胺对血脑屏障通透性的影响。人工脑脊液灌流血管的平均阻力为1800欧米伽厘米(2)，表明血管屏障紧密，离子通透性极低。在单血管连续测量的配对实验中，在洗脑的溶液中加入10(-3)M的5-羟色胺对阻力没有明显影响，而组胺和缓激肽在10(-4)M的浓度下，都能引起阻力的快速和可逆的下降。在10(-4)M组胺和缓激肽中，平均阻力分别为408和505欧米加厘米(2)，大约50%的血管阻力小于250欧米加厘米(2)，而对照组为12%，这表明血脑屏障漏水，不能维持正常的脑离子稳态。组胺和缓激肽具有相似的剂量-反应关系，在20~50 mU M范围内作用最大。因此，组胺和缓激肽作用于脑内皮细胞膜，介导血脑屏障的开放。这些结果支持组胺和缓激肽在脑水肿形成中的作用。
The effect of histamine, bradykinin and serotonin on blood-brain barrier permeability was investigated using in situ measurement of transendothelial electrical resistance in pial microvessels of anaesthetized rats. Mean resistance of vessels superfused with artificial cerebrospinal fluid was 1800 Omega cm(2), indicating a tight barrier with extremely low ion permeability. In paired experiments from continuous measurements in single vessels, addition of 10(-3) M serotonin to the solution bathing the brain had no marked effect on resistance, whereas both histamine and bradykinin, applied at a concentration of 10(-4) M, caused a rapid and reversible decrease in resistance. Mean resistance was 408 and 505 Omega cm(2) in 10(-4) M histamine and bradykinin, respectively, and approximately 50% of vessels had a resistance less than 250 Omega cm(2), compared to 12% in controls, indicating a leaky blood-brain barrier that is not capable of normal brain ion homeostasis. Histamine and bradykinin had similar dose-response relations, and a maximal effect was observed between 20 and 50 mu M Thus, histamine and bradykinin act at the abluminal (brain-facing) membranes of the cerebral endothelium to mediate blood-brain barrier opening. These results support a role for histamine and bradykinin in brain oedema formation.