Effect of free radicals on the permeability of the blood brain barrier - Using in vitro blood brain barrier model of human-SOD transgenic mouse

T. Kondo, S. Imaizumi, I. Kato, M. A. Deli, F. Joo, P. H. Chan, C. J. Epstein, T. Yoshimoto

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Free radicals have been implicated in pathogenesis of vasogenic edema caused by post-ischemic reperfusion injury. It has been reported that Cu-Zn superoxide dismutase transgenic mouse (tg-mouse) which is overexpressing Cu-Zn SOD, prevents post ischemic brain edema and decreases infarct size in middle cerebral artery occlusion model. To investigate the effects of free radicals and free radical scavengers on the permeability of the blood-brain barrier (BBB), we established in vitro BBB model, using cultured brain endothelial cells (BECs) which were extracted from the tg-mice and non tg-mice (control). To make the BBB model, the BECs were cultured on the membrane which has 0.45 μm pores. After cells became confluent, the electrical resistance across the cell monolayer, which reflects the para-cellular flux of ionic molecules, was measured. The BBB model of the tg-mouse were incubated with menadione (Vitamin K3, intracellular O2- producing agent), and the segmental changes of the electrical resistance through the monolayer were compared with those of the control. Moreover, to investigate the effect of the ironic ions which influence the metabolism of free radicals, desferroxamine mesylate (Fe chelating agent) was added to the BBB models before menadione treatment. The cultured brain endothelial cells of tg-mouse has 1.7 times higher SOD activity than that of the control. In the menadione treatment, it showed a significant decrease of electrical resistance in the tg-mouse earlier than that of the control. Desferroxamine mesylate inhibited the early decrease of electrical resistance in the tg-mouse, which was mediated by the menadione treatment. This results indicate the possibility, that the augmented H2O2 which metabolized with the SOD, and OH radical which is induced by the ironic ions, affect the permeability of the BBB, because the H2O2 scavenging enzyme, such as catalase and glutathione peroxidase, are decreasing in this BBB model.

Original languageEnglish
Pages (from-to)1155-1161
Number of pages7
JournalBrain and Nerve
Volume46
Issue number12
Publication statusPublished - Jan 1 1994

Keywords

  • blood-brain barrier
  • brain endothelial cells
  • superoxide dismutase
  • transgenic mouse

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kondo, T., Imaizumi, S., Kato, I., Deli, M. A., Joo, F., Chan, P. H., Epstein, C. J., & Yoshimoto, T. (1994). Effect of free radicals on the permeability of the blood brain barrier - Using in vitro blood brain barrier model of human-SOD transgenic mouse. Brain and Nerve, 46(12), 1155-1161.