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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Aminoquinolines, Animals, Bile Ducts, Blood-Brain Barrier, Chenodeoxycholic Acid, Cholestasis, Deoxycholic Acid, Disease Models, Animal, Endothelial Cells, Ligation, Male, Microvessels, Occludin, Permeability, Phosphorylation, Pyrimidines, RNA, Messenger, Rats, Rats, Sprague-Dawley, Tight Junctions, Tissue Culture Techniques, Zonula Occludens-1 Protein, Zonula Occludens-2 Protein, rac1 GTP-Binding Protein.
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Do bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanisms? Context: The blood brain barrier tightly regulates the passage of molecules into the brain and becomes leaky following obstructive cholestasis. The aim of this study was to determine if increased serum bile acids observed during cholestasis permeabilize the blood brain barrier. Rats underwent bile duct ligation or deoxycholic or chenodeoxycholic acid injections and blood brain barrier permeability assessed. In vitro, the permeability of rat brain microvessel endothelial cell monolayers, the expression and phosphorylation of occludin, ZO-1 and ZO-2 as well as the activity of Rac1 was assessed after treatment with plasma from cholestatic rats, or bile acid treatment, in the presence of a Rac1 inhibitor. Blood brain barrier permeability was increased in vivo and in vitro following bile duct ligation or treatment with bile acids. Associated with the bile acid-stimulated increase in endothelial cell monolayer permeability was elevated Rac1 activity and increased phosphorylation of occludin. Pretreatment of endothelial cell monolayers with a Rac1 inhibitor prevented the effects of bile acid treatment on occludin phosphorylation and monolayer permeability.
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These data suggest that increased circulating serum bile acids may contribute to the increased permeability of the blood brain barrier seen during obstructive cholestasis via disruption of tight junctions. Final Decision: yes