Hypoxia dramatically increases the nonspecific transport of blood-borne proteins to the brain.
Increased cerebrovascular permeability is an important factor for the development of cerebral edema. To investigate the effect of hypoxia on the transport of blood-borne proteins to the brain, we used a cell culture model of the blood-brain barrier (BBB) consisting of a coculture of brain capillary endothelial cells and astrocytes that closely mimics the in vivo situation. The permeability of albumin, a marker of the nonspecific transcellular route, is extremely low in this in vitro model of the BBB. After hypoxia, a huge increase in the permeability of albumin is detected. Despite the opening of the tight junctions already demonstrated after hypoxia, the increase in the permeability of albumin is mainly attributed to an increase of the non-specific vesicular transport in the cell, attested by the temperature dependence of the phenomenon and the visualization of labeled apotransferrin in the cytoplasm. The increase of this pathway could participate in the development of brain edema during hypoxia.
Plateel
M
M
INSERM U. 325-SERLIA, Institut Pasteur de Lille, France.
Teissier
E
E
Cecchelli
R
R
D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply* / Q000166:cytology; D002196:Capillaries / Q000378:metabolism / Q000648:ultrastructure; D015687:Cell Hypoxia / Q000502:physiology; D002478:Cells, Cultured / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate; D000860:Hypoxia / Q000503:physiopathology*; D012709:Serum Albumin / Q000493:pharmacokinetics*; D013696:Temperature; D019108:Tight Junctions / Q000378:metabolism; D014316:Tritium
D001798:Blood Proteins; D012709:Serum Albumin; D014316:Tritium; D016650:Fluorescein-5-isothiocyanate