EFFECTS OF BARBITURATES ON HYPOXIC CULTURES OF BRAIN-DERIVED MICROVASCULAR ENDOTHELIAL-CELLS

An in vitro model of the blood-brain barrier (BBB) consisting of porci ne brain derived microvascular endothelial cells (BMEC) seeded onto co llagen-coated polycarbonate membranes was used to investigate the effe cts of the barbiturates, methohexital and thiopental, on permeability properties of the endothelial cell monolayer under hypoxia. The permea bility of cultured BMEC to ions and sucrose increased significantly du ring 6 h of hypoxia in a reversible manner. Cells were resistant to hy poxia for up to 24 h, but 48 h resulted in marked damage as assessed b y the release of lactate dehydrogenase activity into the culture mediu m. The hypoxia-induced increase of the permeability was unchanged in t he presence of superoxide dismutase (SOD) and catalase. Methohexital a nd thiopental decreased the hypoxia-induced permeability increase in a concentration-dependent manner and permeability changes were abolishe d completely at the barbiturate concentration of 50 mu g/ml. The barbi turates had no effect on the intracellular cAMP content which started to decline after 3 h of hypoxia. Results suggest that barbiturates at high concentrations might be able to prevent permeability changes of t he BBB during cerebral ischemia.