Hypoxia and reoxygenation of a cellular barrier consisting of brain capillary endothelial cells and astrocytes - Pharmacological interventions

Blood-brain barrier (BBB) has been neglected in pharmacological interventions of ischemic brain although it can be reached easily after systemic administration of a drug. Brain capillary endothelial cells (BCEC) may contain NMDA receptors so that the antagonist MX-801 was studied to protect BBB function. Oxygen deficiency is a main limitation during ischemia known to generate free radicals. During hypoxia and reoxygenation, an increase of radical-induced lipid peroxidation in both BCEC and astrocytes (AC) was found, accompanied by disturbances of BBB function. Therefore, the radical scavenging lazaroid U83836E was also studied. Upon hypoxia, the permeability of the barrier (BCEC and AC, cultured separately on the two sides of a filter) increased. This effect was intensified during the following reoxygenation. MK-801 and U83836E reduced the hypoxia-induced increase of permeability.