The function of the blood-brain barrier (BBB) can be impaired by free radic
als. Since free radicals have only a limited diffusion capacity, we tested
the possibility whether one of the major secondary lipid peroxidation produ
ct - 4-hydroxynonenal, is able to influence the permeability of the BBB. Th
erefore, we established an in vitro BBB model and tested its capacity to de
grade 4-hydroxynonenal. Although, endothelial cells and astrocytes, posses
the ability to degrade 4-hydroxynonenal the aldehyde is able to increase th
e 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 conclu
ded that 4-hydroxynonenal is able to impair the BBB function via the decrea
se of reduced glutathione. (C) 2001 Elsevier Science Ireland Ltd. All right
s reserved.