4-Hydroxynonenal impairs the permeability of an in vitro rat blood-brain barrier

The function of the blood-brain barrier (BBB) can be impaired by free radicals. Since free radicals have only a limited diffusion capacity, we tested the possibility whether one of the major secondary lipid peroxidation product - 4-hydroxynonenal, is able to influence the permeability of the BBB. Therefore, we established an in vitro BBB model and tested its capacity to degrade 4-hydroxynonenal. Although, endothelial cells and astrocytes, possess the ability to degrade 4-hydroxynonenal the aldehyde is able to increase the permeability of the BBB. Since aldehydic lipid peroxidation products are metabolized via conjugation with glutathione we proofed that a decrease in glutathione is also able to increase the permeability of the BBB. We concluded that 4-hydroxynonenal is able to impair the BBB function via the decrease of reduced glutathione.