Nag S
Division of Neuropathology, Toronto Hospital, Ontario, Canada.
Acta Neuropathol. 1995;90(5):454-60. doi: 10.1007/BF00294805.
The role of the cytoskeletal elements, microfilaments and microtubules in cerebral endothelial permeability to protein during steady states was investigated by studies of cerebrovascular permeability to horseradish peroxidase (HRP) in rats pretreated with cytochalasin B or colchicine, agents known to disrupt microfilaments and microtubules, respectively. In addition, the effect of colchicine pretreatment on the alterations in cerebrovascular permeability that occur in acute hypertension were studied. Rats infused with cytochalasin B showed increased cerebrovascular permeability to HRP in multifocal areas of the ipsilateral hemisphere. Most of the permeable vessels were arterioles; however, capillaries and venules also showed increased permeability. Ultrastructural studies of permeable vessels showed HRP in all layers of vessel walls and in endothelial and smooth muscle cell pinocytotic vesicles, which were increased in number. Although segments of interendothelial spaces were labeled by tracer, continuous labeling of interendothelial spaces from the luminal to the abluminal end was not seen and tight junctions were not disrupted. Normotensive rats pretreated with colchicine showed no alteration in cerebrovascular permeability to HRP. Colchicine pretreatment attenuated the permeability alterations that were observed in acutely hypertensive rats. This study demonstrates that integrity of endothelial actin filaments is important for maintenance of the blood-brain barrier to protein during steady states since increased permeability occurred in the presence of an actin disrupting agent. The microtubular network had no demonstrable role during steady states; however, disruption of the microtubular network had a protective effect and prevented the development of alterations in permeability to protein in acute hypertension.
通过对用细胞松弛素B或秋水仙碱预处理的大鼠进行脑血管对辣根过氧化物酶（HRP）通透性的研究，探讨了细胞骨架成分微丝和微管在稳态期间脑内皮对蛋白质通透性中的作用。已知细胞松弛素B和秋水仙碱分别破坏微丝和微管。此外，还研究了秋水仙碱预处理对急性高血压时脑血管通透性改变的影响。注入细胞松弛素B的大鼠同侧半球多灶区对HRP的脑血管通透性增加。大多数通透性增加的血管是小动脉；然而，毛细血管和小静脉的通透性也增加。对通透性增加的血管进行超微结构研究发现，血管壁各层以及内皮细胞和平滑肌细胞的胞饮小泡中均有HRP，且胞饮小泡数量增加。虽然示踪剂标记了内皮细胞间隙的部分区域，但未观察到从管腔到管腔外端内皮细胞间隙的连续标记，紧密连接也未被破坏。用秋水仙碱预处理过的正常血压大鼠对HRP的脑血管通透性无改变。秋水仙碱预处理减轻了急性高血压大鼠中观察到的通透性改变。本研究表明，内皮肌动蛋白丝的完整性对于稳态期间血脑屏障对蛋白质的维持很重要，因为在存在肌动蛋白破坏剂的情况下通透性增加。微管网络在稳态期间没有明显作用；然而，微管网络的破坏具有保护作用，并防止了急性高血压时蛋白质通透性改变的发生。
