Diseases and disorders Abstract Pivotal to brain development and function is an intact blood-brain barrier BBBwhich acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. We report that germ-free micebeginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora.
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Abstract Disruption of tight junctions TJs perturbs endothelial barrier function and promotes inflammation. Eicosanoid, Endothelial Cell, Lipoxygenase Pathway, Signal Transduction, Tight Junctions Introduction Atherosclerosis is one of the leading causes of death and disability in the world 12.
It is characterized by the presence of lipid-laden macrophages and smooth muscle cells as well as other inflammatory cells in the vessel wall 34.
Furthermore, HETE was found to be the predominant eicosanoid formed in the arteries of Watanabe heritable hyperlipidemic and cholesterol-fed rabbits 12 Besides its role in the conversion of AA, LO1 has been shown to oxidize low density lipoprotein LDLa crucial mediator of atherogenesis 14 Furthermore, overexpression of human LO1 in the endothelium of LDL receptor-deficient mice exacerbated early atherosclerosis Thus, there is a convincing body of evidence for the role of LO1 in atherogenesis.
The endothelium forms a continuous inner lining of the blood vessels and provides a selective nonthrombogenic permeability barrier between the vascular wall and blood 19 Tight junctions TJs play a crucial role in the regulation of endothelial barrier function, and their disruption leads to increased paracellular permeability and endothelial dysfunction 21 Endothelial dysfunction is generally regarded as the initial step in atherosclerotic plaque formation 23 Growth factor-reduced Matrigel was obtained from BD Biosciences.
The adenovirus was purified by cesium chloride gradient ultracentrifugation as described previously Adherent cells macrophages were used for transmigration assay. HUVECs between 6 and 10 passages were growth-arrested by incubating in medium for 12 h and used to perform the experiments unless otherwise indicated.
After treatments, cells were trypsinized, and trypan blue solution 0. The cell viability was expressed as percentage of viable cells. Western Blot Analysis Western blot analysis was performed as described previously To ensure complete rupture of cell membranes, cells were sonicated at a 40 MHz pulse for 40 s followed by centrifugation at rpm for 10 min.
The beads were collected by centrifugation at rpm for 1 min, washed in lysis buffer, and heated in Laemmli sample buffer for 10 min, and the released proteins were resolved on SDS-PAGE and immunoblotted with the desired antibodies. Then the cells were incubated with mouse anti-ZO-1 antibodies in combination with rabbit anti-occludin antibodies followed by goat anti-mouse and goat anti-rabbit secondary antibodies conjugated with Alexa Fluor and Alexa Fluorrespectively, counter-stained with Hoechst 1:In conclusion, the interaction between pericytes and endothelial cells can regulate the formation of tight junctions in hyaloid vessels devoid of astrocytes.
We demonstrate the expression of tight junction proteins, ZO-1 and occludin, in hyaloid vessels during the early postnatal periods. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood–brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules.
The Role of Circulating Tight Junction Proteins in Evaluating Blood Brain Barrier Disruption following Intracranial Hemorrhage XiaoyangJiao, 1 PingHe, 2 YazhenLi, 1 ZhichengFan, 1 MengyaSi, 1 QingdongXie, 1 in endothelial tight junction can facilitate capillary leakage.
Objective: To evaluate the significance of circulating tight-junction (TJ) proteins as predictors of hemorrhagic transformation (HT) in ischemic stroke patients. Methods: We examined consecutive ischemic stroke patients, % of whom had clinically evident HT.
In brain microvascular endothelial cells, membrane-associated guanylate kinase-like (MAGUK) proteins are involved in clustering of tight junction protein complexes to the cell membrane. Three MAGUK proteins have been identified at the tight junction: ZO-1, -2, and Tight junction proteins occludin, claudin (1, 3, 5, and 12), and junctional adhesion molecule (JAM-A, B, and C) are found on brain microvessel endothelial cells (1, ).
Tight junction proteins occludin, claudin (1, 3, 5, and 12), and junctional adhesion molecule (JAM-A, B, and C) are found on brain microvessel endothelial cells (1, ). Molecular Regulation of Endothelial Cell Tight Junctions Fig. 1. Proposed interactions between claudins at the tight junction. The claudin proteins. The tight junctions between endothelial cells are responsible for the barrier function. Occludin was the first integral membrane protein found to be exclusively localized within the tight junctions.