Intra-abdominal hypertension causes reversible blood-brain barrier disruption

Abstract

Previous studies have shown that intra-abdominal hypertension (IAH) has detrimental effects on organ function and is associated with significantly increased morbidity and mortality. IAH has also been shown to increase intracranial pressure. The exact mechanism is not known. This study tests the effect of an acute increase in intra-abdominal pressure on the permeability of the blood-brain barrier (BBB) in mice. Male CD-1 mice weighing 30 g to 38 g were used. Mice in experimental groups underwent either 4 hours of IAH or 4 hours of IAH followed by 1 hour of decompression (DC). A set of control mice were anesthetized for either 4 hours or 5 hours. Femoral artery cannulation was used for blood pressure monitoring. IAH was induced by intraperitoneal infusion of mineral oil to a pressure of 20 mm Hg. DC was performed through an incision in the anterior abdominal wall. BBB integrity was determined by extravasation of 2% Evans blue (EB) dye administered through the femoral vein 1 hour before the mice were killed. BBB permeability was quantified by the EB extravasation method. EB content in brain tissue was higher in the IAH 4-hour group (n = 12) compared with their control group (n = 4; p < 0.05), indicating increased permeability of BBB. In the IAH 4-hour + DC 1-hour group (n = 6), EB content in brain tissue was not significantly higher than their respective control group (n = 6). IAH of 20 mm Hg in mice for 4 hours caused increased BBB permeability. This endothelial barrier dysfunction is reversed by abdominal DC.