Hyperglycemic Condition Causes Pro-Inflammatory and Permeability Alterations Associated with Monocyte Recruitment and Deregulated NFκB/PPARγ Pathways on Cerebral Endothelial Cells: Evidence for Polyphenols Uptake and Protective Effect

Hyperglycemia alters the function of cerebral endothelial cells from the blood-brain barrier, increasing the risk of cerebrovascular complications during diabetes. This study evaluated the protective effect of polyphenols on inflammatory and permeability markers on bEnd3 cerebral endothelial cells exposed to high glucose concentration. Results show that hyperglycemic condition increased nuclear factor kappa B (NFκB) activity, deregulated the expression of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-10 (IL-10) and endothelial-leukocyte adhesion molecule (E-selectin) genes, raised MCP-1 secretion and elevated monocyte adhesion and transendothelial migration. High glucose decreased occludin, claudin-5, zona occludens-1 (ZO-1) and zona occludens-2 (ZO-2) tight junctions production and altered the endothelial permeability. Characterized polyphenolic extracts from the French medicinal plants Antirhea borbonica, Ayapana triplinervis, Dodonaea viscosa and Terminalia bentzoe, and their major polyphenols quercetin, caffeic, chlorogenic and gallic acids limited the pro-inflammatory and permeability alterations caused by high glucose. Peroxisome proliferator-activated receptor gamma (PPARγ) agonist also attenuated these damages while PPARγ antagonist aggravated them, suggesting PPARγ protective action. Interestingly, polyphenols improved PPARγ gene expression lowered by high glucose. Moreover, polyphenols were detected at the intracellular level or membrane-bound to cells, with evidence for breast cancer resistance protein (BCRP) efflux transporter role. Altogether, these findings emphasize the ability of polyphenols to protect cerebral endothelial cells in hyperglycemic condition and their relevance for pharmacological strategies aiming to limit cerebrovascular disorders in diabetes.

Evaluation of Permeability Changes in a Carbonate Rock under Carbonate Water Flow

Carbon dioxide (CO2) injection in reservoirs promotes reactions which depend on rock nature, brine composition, partial pressure of CO2, reservoir temperature and pressure among other conditions. The reactions may cause changes in the petrophysics properties, including porosity and permeability, that are important parameters to the fluid flow. The present study focus on the effects of carbonated brine injection in carbonate rocks similar to pre salt reservoirs. The effects are evaluated through the changes of the rock absolute permeability provoked by the acidic action of the injected fluid. Experiments were designed to detail permeability changes along the length of a long carbonate core using using a coreholder equipped with multiple pressure taps. The experiments were conducted in dynamic regime, at the temperature of 22°C and at the mean pressure of 2,000 psi, at flow rates of 0.5; 1 and 2 cc/min. The results show significant permeability alterations at the different segments of the sample, which are also highly dependent on the injection rate.