Effect of MK-801 and U83836E on a porcine brain capillary endothelial cell barrier during hypoxia.
The present study investigated the influence of MK-801 (N-methyl-D-aspartate receptor antagonist) and U83836E (antioxidative aminosteroid) on the permeability of sodium fluorescein through a cell barrier during hypoxia (2 h 95% N2/5% CO2). The barrier consisted of porcine brain capillary endothelial cells and of cerebral rat astrocytes cultivated on two sides of a filter. After hypoxia, the permeation of fluorescein was significantly increased (10.2 +/- 1.5 x 10(-3) cm/min, P < 0.001) compared to the normoxic control (2 h 95% O2/5% CO2, 1.8 +/- 0.6 x 10(-3) cm/min). The hypoxia-enhanced permeation was significantly (P < 0.05) reduced by 10 microM MK-801 (2.0 +/- 0.5 x 10(-3) cm/min) and 10 microM U83836E (3.1 +/- 1.3 x 10(-3) cm/min). The results demonstrate, for the first time in a cell culture system, that hypoxia impairs brain endothelial barrier function, and that this enhanced permeability can be influenced pharmacologically. It is concluded that two distinct pathogenic mechanisms are involved in hypoxic cerebral endothelial cell injury, and that cerebroprotection afforded by these agents may result, in part, from reductions in edema secondary to improved blood-brain barrier function.
Giese
H
H
Forschungsinstitut für Molekulare Pharmacokologie Forschungsverbund Berlin, Germany.
Mertsch
K
K
Blasig
I E
IE
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000166:cytology; D002196:Capillaries; D002478:Cells, Cultured; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019793:Fluorescein; D005452:Fluoresceins; D016166:Free Radical Scavengers / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
D002839:Chromans; D005452:Fluoresceins; D016166:Free Radical Scavengers; D010879:Piperazines; C066382:U 78517F; D016291:Dizocilpine Maleate; D019793:Fluorescein