NITRIC-OXIDE PROTECTS BLOOD-BRAIN-BARRIER IN-VITRO FROM HYPOXIA REOXYGENATION-MEDIATED INJURY/

A cell culture model of blood-brain barrier (BBB, coculture of rat bra in endothelial cells with rat astrocytes) was used to investigate the effect of nitric oxide ((NO)-N-.) on the damage of the BBB induced by hypoxia/reoxygenation (H/R), Permeability coefficient of fluorescein a cross the endothelium was used as a marker of BBB tightness. The perme ability coefficient increased 5.2 times after H/R indicating strong di sruption of the BBB, The presence of the (NO)-N-. donor S-nitroso-N-ac etylpenicillamine (SNAP, 30 mu M), authentic (NO)-N-. (6 mu M) or supe roxide dismutase (50 units/ml) during H/R attenuated H/R-induced incre ase in permeability. 30 mu M SNAP or 6 mu M (NO)-N-. did not influence the function of BBB during normoxia, however, severe disruption was o bserved using 150 mu M of SNAP and more than 24 mu M of (NO)-N-.. Afte r H/R of endothelial cells, the content of malondialdehyde (MDA) incre ased 2.3 times indicating radical-induced peroxidation of membrane lip ids, 30 mu M SNAP or 6 mu M authentic (NO)-N-. completely prevented MD A formation, The results show that (NO)-N-. may effectively scavenge r eactive oxygen species formed during H/R of brain capillary endothelia l cells, affording protection of BBB at the molecular and functional l evel. (C) 1998 Federation of European Biochemical Societies.