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 cu lture model of the blood-brain barrier (BBB) consisting of a coculture of brain capillary endothelial cells and astrocytes that closely mimi cs the in vivo situation. The permeability of albumin, a marker of the nonspecific transcellular route, is extremely low in this in vitro mo del of the BBB. After hypoxia, a huge increase in the permeability of albumin is detected. Despite the opening of the tight junctions alread y demonstrated after hypoxia, the increase in the permeability of albu min is mainly attributed to an increase of the nonspecific vesicular t ransport in the cell, attested by the temperature dependence of the ph enomenon and the visualization of labeled apotransferrin in the cytopl asm. The increase of this pathway could participate in the development of brain edema during hypoxia.