Emerging molecular mechanisms of brain tumour oedema.
A common property of brain tumours is their ability to cause oedema in the surrounding brain. Oedema forms as a result of a leaky blood-tumour barrier and persists when the brain fails to clear the excess fluid. It is a significant source of morbidity and mortality. The principal anatomical component of the blood-brain barrier is the endothelial tight junction which opens in glioma microvessels. Multiple tight junction proteins have recently been identified, such as occludin, claudin, ZO-1, ZO-2 and ZO-3. We propose a model to explain tight junction opening in gliomas based on vascular endothelial growth factor secretion and loss of tight junction inducing factor production by tumour cells. The level of expression of the water channel aquaporin-4 in peritumoural astrocytes may determine the rate of oedema fluid clearance. The identification of the molecular mechanisms of brain tumour oedema may allow the design of novel anti-oedema medications.
Papadopoulos
M C
MC
Department of Neurosurgery, Atkinson Morley's Hospital, Copse Hill, London SW20 0NE, UK. MPapadopoulos@compuserve.com
Saadoun
S
S
Davies
D C
DC
Bell
B A
BA
D000818:Animals; D001254:Astrocytoma / Q000150:complications / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier / Q000235:genetics*; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics*; D001932:Brain Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D002199:Capillary Permeability; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005909:Glioblastoma / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism / Q000648:ultrastructure; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D008854:Microscopy, Electron; D010766:Phosphorylation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D005938:Glucocorticoids; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors