The influence of oxygen free radicals on the permeability of the monolayer of cultured brain endothelial cells.
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-micron 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.
Imaizumi
S
S
Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan.
Kondo
T
T
Deli
M A
MA
Gobbel
G
G
Joó
F
F
Epstein
C J
CJ
Yoshimoto
T
T
Chan
P H
PH
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply*; D002199:Capillary Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005609:Free Radicals; D015870:Gene Expression; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000494:pharmacology*; D014812:Vitamin K / Q000494:pharmacology
D005609:Free Radicals; D013481:Superoxides; D014812:Vitamin K; D013482:Superoxide Dismutase; D003676:Deferoxamine