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-asp artate receptor antagonist) and U83836E (antioxidative aminosteroid) o n the permeability of sodium fluorescein through a cell barrier during hypoxia (2 h 95% N-2/5% 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% O-2/5% CO2, 1.8 +/- 0.6 x 1 0(-3) cm/min). The hypoxia-enhanced permeation was significantly (P < 0.05) reduced by 10 mu M MK-801 (2.0 +/- 0.5 x 10(-3) cm/min) and 10 m u M U83836E (3.1 +/- 1.3 x 10(-3) cm/min). The results demonstrate, fo r 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 pat hogenic mechanisms are involved in hypoxic cerebral endothelial cell i njury, and that cerebroprotection afforded by these agents may result, in part, from reductions in edema secondary to improved blood-brain b arrier function.