Molecular mechanisms of brain tumor edema

Despite their diverse histological types, most brain tumours cause brain oedema, which is a significant cause of patient morbidity and mortality. Brain tumour oedema occurs when plasma-like fluid enters the brain extracellular space through impaired capillary endothelial tight junctions in tumours....

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Bibliographic Details
Published in:Neuroscience 2004, Vol.129 (4), p.1009-1018
Main Authors: Papadopoulos, M.C., Saadoun, S., Binder, D.K., Manley, G.T., Krishna, S., Verkman, A.S.
Format: Article
Language:English
Subjects:
Animals
aquaporin
Aquaporins - genetics
Aquaporins - metabolism
Blood-Brain Barrier - physiopathology
blood–brain barrier
Brain Edema - drug therapy
Brain Edema - etiology
Brain Edema - physiopathology
Brain Neoplasms - complications
Brain Neoplasms - physiopathology
Cell Membrane Permeability - genetics
Claudin-1
Endothelial Cells - metabolism
Endothelial Cells - ultrastructure
Humans
Membrane Proteins - genetics
Membrane Proteins - metabolism
tight junction
Tight Junctions - genetics
Tight Junctions - metabolism
Tight Junctions - ultrastructure
vasogenic edema
water channel
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Summary:Despite their diverse histological types, most brain tumours cause brain oedema, which is a significant cause of patient morbidity and mortality. Brain tumour oedema occurs when plasma-like fluid enters the brain extracellular space through impaired capillary endothelial tight junctions in tumours. Under-expression of the tight junction proteins occludin, claudin-1 and claudin-5 are key molecular abnormalities responsible for the increased permeability of tumour endothelial tight junctions. Recent evidence suggests that the membrane water channel protein aquaporin-4 (AQP4) also plays a role in brain tumour oedema. AQP4-deficient mice show remarkably altered brain water balance after various insults, including brain tumour implantation. AQP4 expression is strongly upregulated around malignant human brain tumours in association with reduced extracellular volume, which may restrict the flow of extracellular fluid from the tumour bed into the brain parenchyma. Elimination of excess fluid leaking into brain parenchyma requires passage across three AQP4-rich barriers: a) the glia limitans externa, b) the glia limitans interna/ependyma, and c) the blood–brain barrier. Modulation of the expression and/or function of endothelial tight junction proteins and aquaporins may provide novel therapeutic options for reducing brain tumour oedema.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2004.05.044