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Titolo:
Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy
Autore:
Rapoport, SI;
Indirizzi:
NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA NIA BethesdaMD USA 20892 ysiol & Metab Sect, NIH, Bethesda, MD 20892 USA
Titolo Testata:
EXPERT OPINION ON INVESTIGATIONAL DRUGS
fascicolo: 10, volume: 10, anno: 2001,
pagine: 1809 - 1818
SICI:
1354-3784(200110)10:10<1809:AIOOOT>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; CAPILLARY ENDOTHELIAL-CELLS; RAT-BRAIN; HYPEROSMOLAR MANNITOL; INTRAARTERIAL CHEMOTHERAPY; INTRACAROTID INJECTION; CEREBRAL ENDOTHELIUM; TIGHT JUNCTIONS; CALCIUM-ION; IN-VIVO;
Keywords:
arabinose; blood-brain barrier; bulk flow; calcium; capillary; chemotherapy; cytoskeleton endothelium; diffusion; mannitol; oedema; osmosis; permeability; rat; shrinkage; tight junctions; tumour;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
94
Recensione:
Indirizzi per estratti:
Indirizzo: Rapoport, SI NIA, Brain Physiol & Metab Sect, NIH, Bldg 10,Rm 6N 202, Bethesda, MD 20892 USA NIA Bldg 10,Rm 6N 202 Bethesda MD USA 20892 sda, MD 20892 USA
Citazione:
S.I. Rapoport, "Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy", EXPERT OP I, 10(10), 2001, pp. 1809-1818

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, boron compounds for neutron capture therapy, viral vectors for gene therapy and enzymes. Ongoing multi-centre clinical studies suggest that the method, when used with intra-arteriallyadministered anticancer drugs, can prolong survival in patients with malignant brain tumours, with minimal morbidity. However, controlled clinical trials are critical to see if the osmotic procedure with intraarterial drugs enhances survival in brain tumour patients compared with intra-arterial drug alone.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 10:30:22