Cellular and Molecular Neurobiology

, Volume 20, Issue 2, pp 217–230 | Cite as

Osmotic Opening of the Blood–Brain Barrier: Principles, Mechanism, and Therapeutic Applications

  • Stanley I. Rapoport


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 cerebrovascular endothelial cells, with widening of the interendothelial tight junctions to an estimated radius of 200 Å. 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 flow 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.

arabinose mannitol blood–brain barrier brain drug chemotherapy osmosis shrinkage permeability tumor bulk flow tight junctions capillary 


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© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Stanley I. Rapoport
    • 1
  1. 1.Section on Brain Physiology and MetabolismNational Institute on Aging, National Institutes of HealthBethesda

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