Pathway across blood-brain barrier opened by the bradykinin agonist, RMP-7
Pathway across blood-brain barrier opened by the bradykinin agonist, RMP-7
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DOI：
10.1016/0006-8993(95)01143-9
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发表时间：
1995-12-24
期刊：
影响因子：
2.9
通讯作者：
Brightman, MW
中科院分区：
文献类型：
--
作者：
Sanovich, E;Bartus, RT;Brightman, MW
当新的缓激肽激动剂RMP-7开放血脑屏障时，La(相对分子质量139)通过脑内皮细胞的途径被描绘出来。Balb C小鼠经颈静脉注入LaCl3+或不+RMP-7(5mug/kg)。10分钟后，用醛固定大脑并对其进行电子显微镜检查。通过计算LaCl3穿透的连接数来评估内皮细胞间连接的通畅性。示踪剂穿透约25%的微血管连接，在RMP-7组约58%，每条血管也有更多的连接被穿透。然后，在RMP-7组，LaCl3穿透了大约20%的微血管，而对照组的这一比例为0.50%。在RMP-7组和对照组中，示踪剂从基底板进入血管周围间隙的比例分别为13%和0.07%。RMP-7组仅有极少的内吞陷窝或小泡被标记，因此LaCl3不会通过细胞转运进入内皮细胞。因此，在RMP-7处理的动物中，示踪剂穿透的紧密连接的数量增加，并扩散到内皮周围的基底板和间质裂隙，表明细胞旁的渗出途径。
The route taken by lanthanum (MW 139) across cerebral endothelium was delineated when the blood-brain barrier was opened by RMP-7, a novel bradykinin agonist. Balb C mice were infused through a jugular vein with LaCl3 with or without RMP-7 (5 mu g/kg). Ten minutes later, the brains were fixed with aldehydes and processed for electron microscopy. The patency of the junctions between endothelial cells was estimated by counting the number of junctions penetrated by LaCl3. Tracer penetrated the junctions in about 25% of microvessels in vehicle infused, control mice and about 58% in the RMP-7 group, where more junctions per vessel were also penetrated. The LaCl3 then penetrated the basal lamina in about 20% of all microvessels in the RMP-7 group, versus 0.50% in the control group. From the basal lamina, the tracer entered perivascular spaces in about 13% of all microvessels in the RMP-7 group and about 0.07% in the controls. Very few endocytic pits or vesicles in the RMP-7 group were labeled, so LaCl3 did not cross endothelium by transcytosis. The increased number of tight junctions penetrated by tracer and its spread into periendothelial basal lamina and interstitial clefts indicated, therefore, a paracellular route of exudation in the RMP-7 treated animals.