Effects of hypoxia on an in vitro blood-brain barrier

Using a cell culture model of the BBB, we investigated the brain capillary ECs response to hypoxia. ECs contain the same free-radical protecting enzymes and glutathione as isolated capillaries. These anti-oxidant enzymes and GSH are not induced by astrocytes. These results clearly show that ECs could be a relevant model to study the effects of hypoxia at the BBB level. In the time course of hypoxia, free radical detoxifying enzymes and GSH level decrease. Concomittant rearrangements of F-actin of the ECs and a decrease in the ATP level might explain the paracellular permeability increase of the monolayer. An apoptotic process is detected by in situ end labeling of DNA. This suggests that hypoxia alters some functions of the ECs monolayer and increases the susceptibility of the BBB to further oxidative damages.