Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy
- 1 October 2001
- journal article
- review article
- Published by Informa Healthcare in Expert Opinion on Investigational Drugs
- Vol. 10 (10), 1809-1818
- https://doi.org/10.1517/13543784.10.10.1809
Abstract
The blood-brain barrier (BBB) to water-soluble drugs and macromolecules can be opened in vivo by infusing a hypertonic solution of arabinose or mannitol into the carotid artery for 30 sec. Opening involves widening of tight junctions between endothelial cells of the cerebrovasculature and is mediated by endothelial cell shrinkage, vascular dilatation associated with removal of water from brain, and modulation of the contractile state of the endothelial cytoskeleton and junctional proteins by increased intracellular calcium. A 10-fold increase in BBB permeability to intravascular substances, lasting about 10 min following osmotic exposure, reflects both increased diffusion and bulk fluid flow from blood into brain. Furthermore, recent evidence indicates that the duration of peak BBB opening can be extended beyond 30 min, by pre-treatment with a Na+/Ca2+ channel blocker. In experimental animals, the osmotic method has been used to grant wide access to brain of water-soluble drugs, peptides, antibodies, boro...Keywords
This publication has 62 references indexed in Scilit:
- Cell adhesion, cell junctions and the blood—brain barrierCurrent Opinion in Neurobiology, 1996
- Modulation of Blood-Brain Barrier PermeabilityJournal of Drug Targeting, 1996
- Antisense Inhibition of Hypertension in the Spontaneously Hypertensive RatHypertension, 1995
- Use of recombinant vectors derived from herpes simplex virus 1 mutant tsK for short-term expression of transgenes encoding cytoplasmic and membrane anchored proteins in postmitotic polarized cortical neurons and glial cells in vitroNeuroscience, 1994
- Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugsCell, 1994
- Tight‐Junctional Modification as the Basis of Osmotic Opening of the Blood‐Brain BarrieraAnnals of the New York Academy of Sciences, 1986
- Hyperosmotic arabinose solutions open the tight junctions between brain capillary endothelial cells in tissue cultureBrain Research, 1984
- Ionic lanthanum passage across cerebral endothelium exposed to hyperosmotic arabinoseActa Neuropathologica, 1983
- Osmotic opening of tight junctions in cerebral endotheliumJournal of Comparative Neurology, 1973
- Osmotic Opening of the Blood-Brain Barrier in the Monkey without Associated Neurological DeficitsScience, 1973