Endothelial cell (EC) barrier dysfunction (i.e., increased vascular permeability) is observed in inflammatory states, tumor angiogenesis, atherosclerosis, and both sepsis and acute lung injury. Therefore, agents that preserve vascular integrity have important clinical therapeutic implications. We examined the effects of methylnaltrexone (MNTX), a mu opioid receptor (mOP-R) antagonist, on human ...

Brain microvessels possess barrier structures comprising tight junctions which are critical for the maintenance of central nervous system homeostasis. Brain vascular diseases, such as ischemic stroke damage to blood-brain barrier, increase the vascular permeability, and then lead to vasogenic brain edema. Herein, we examined whether angiopoietin-1 (Ang-1) could regulate zonula occludens-2 (ZO-2...

We investigated the effects of intravenous application of nimodipine on the neurophysiologic, biochemical, and morphologic consequences of 15 minutes of global cerebral ischemia in seven rabbits. In vivo dialysis of the hippocampus was used to determine changes in extracellular concentrations of extracellular calcium and amino acids and blood-brain barrier permeability. Ischemia without treatme...

Increased endothelial permeability contributes to the morbidity and mortality associated with chronic inflammatory diseases, including acute lung injury. Cyclic AMP response element-binding protein (CREB) transcriptional factor induces genes that regulate inflammation and vascular remodeling. However, the role of CREB in regulating endothelial barrier function is unknown. Here, we demonstrate t...

Optic neuritis is an acute inflammatory condition that is highly associated with multiple sclerosis. Currently, the best predictor of future development of multiple sclerosis is the number of T2 lesions visualized by magnetic resonance imaging. Previous research has found abnormalities in the permeability of the blood-brain barrier in normal-appearing white matter of patients with multiple scle...

Angiotensin II (AngII) caused pulmonary microvascular endothelial barrier injury, which induced acute aortic dissection (AAD) combined with acute lung injury (ALI). However, the exact mechanism is unclear. We investigated the role of dephosphorylation of Y685-VE-cadherin in the AngII induced pulmonary microvascular endothelial barrier injury. Mice or pulmonary microvascular endothelial cells (P...

Endothelial cells (ECs), forming a semi-permeable barrier between the interior space of blood vessels and underlying tissues, control such diverse processes as vascular tone, homeostasis, adhesion of platelets, and leukocytes to the vascular wall and permeability of vascular wall for cells and fluids. Mechanisms which govern the highly clinically relevant process of increased EC permeability ar...

To improve the blood-brain barrier permeability of the trypanocidal lead compound 4,4'-bis(imidazolinylamino)diphenylamine (1), five N-alkoxy analogues were synthesized from bis(4-isothiocyanatophenyl)amine and N-alkoxy-N-(2-aminoethyl)-2-nitrobenzenesulfonamides following successive chemical reactions in just one reactor ("one-pot procedure"). This involved: (a) formation of a thiourea interme...

Astragalus membranaceus is widely used to treat stroke and chronic debilitating diseases in China, but the mechanism has not been fully demonstrated to data. In the present study, we, using astragaloside IV, a purified extract from astragalus membranaceus, to a focal cerebral ischemia/reperfusion rat model, aimed to investigate the effect of astragaloside IV on the permeability of the blood-bra...

Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the...