Osmotic opening of the blood-brain barrier: Principles, mechanism, and therapeutic applications
Osmotic opening of the blood-brain barrier: Principles, mechanism, and therapeutic applications
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DOI：
10.1023/a:1007049806660
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发表时间：
2000-04-01
影响因子：
4
通讯作者：
Rapoport, SI
中科院分区：
文献类型：
--
作者：
Rapoport, SI
1.通过颈动脉内输注高渗阿拉伯糖或甘露醇溶液引起的血脑屏障的渗透性开放是由血管内皮细胞的血管舒张和收缩介导的，内皮间紧密连接扩大到估计半径200埃。钙介导的内皮细胞骨架收缩可能促进了这种作用。2.在渗透过程之后，血管内物质的表观血脑屏障渗透性的显著增加（对于小分子为10倍）是由于扩散增加和大量流体如何穿过紧密连接。渗透性效应在10 min内基本逆转。在实验动物中，渗透方法已被用于允许水溶性药物、肽、抗体、用于中子捕获治疗的硼化合物和用于基因治疗的病毒载体广泛进入大脑。该方法也已与抗癌药物一起用于治疗转移性或原发性脑肿瘤患者，取得了一些成功和最小的发病率。
1. Osmotic opening of the blood-brain barrier by intracarotid infusion of a hypertonic arabinose or mannitol solution is mediated by vasodilatation and shrinkage of cerebrovas cular endothelial cells, with widening of the interendothelial tight junctions to an estimated radius of 200 Angstrom. The effect may be facilitated by calcium-mediated contraction of the endothelial cytoskeleton.2. The marked increase in apparent blood-brain barrier permeability to intravascular substances (10-fold for small molecules) following the osmotic procedure is due to both increased diffusion and bulk fluid how across the tight junctions. The permeability effect is largely reversed within 10 min.3. In experimental animals, the osmotic method has been used to grant wide access to the brain of water-soluble drugs, peptides, antibodies, boron compounds for neutron capture therapy, and viral vectors for gene therapy. The method also has been used together with anticancer drugs to treat patients with metastatic or primary brain tumors, with some success and minimal morbidity.