期刊
CELLULAR AND MOLECULAR NEUROBIOLOGY
卷 20, 期 2, 页码 217-230出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1023/A:1007049806660
关键词
arabinose; mannitol; blood-brain barrier; brain; drug; chemotherapy; osmosis; shrinkage; permeability; tumor; bulk flow; tight junctions; capillary
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.
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