Free radicals have been implicated in the pathogenesis of vasogenic brain edema caused by ischemic or traumatic injury. It has been reported that in transgenic mice overexpressing the human CuZn-superoxide dismutase, brain edema is decreased in many cerebral disorders. To investigate the effects of free radicals on the permeability of the blood-brain barrier, we established an in vitro model system of the blood-brain barrier using brain endothelial cells cultivated from transgenic mice and non-transgenic mice. The blood-brain barrier model is originated by a monolayer of brain endothelial cells cultured on a membrane which has 0.45-μm pores. Electrical resistance across the cell monolayer, which reflects the paracellular flux of ionic molecules, was measured. The blood-brain barrier models were incubated with menadione (vitamin K3, an intracellular O2- producing agent), and segmental changes in the electrical resistance across the monolayer were compared between the transgenic and the non-transgenic mice. Superoxide dismutase activity of the cultured brain endothelial cells was 1.7 times higher in the transgenic than in the non-transgenic mice (n = 3, P < 0.001). The electrical resistance was reduced by menadione in the transgenic but not in the non-transgenic mice (n = 7, P < 0.05) in the early stage. Moreover, desferroxamine mesylate (Fe2+ chelating agent) inhibited the menadione-induced early decrease in electrical resistance in the transgenic mice (n = 7, P < 0.05). These results suggest that the permeability of the blood-brain barrier may be affected by hydroxyl radicals and/or peroxynitrite rather than the O2- itself.
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Cell Biology