Search results for "Capillary Permeability"
showing 10 items of 35 documents
Dextran sulfate sodium leads to chronic colitis and pathological angiogenesis in Endoglin heterozygous mice
2010
Pathological angiogenesis is an intrinsic component of chronic intestinal inflammation, which results in remodeling and expansion of the gut microvascular bed. Endoglin is essential for endothelial cell function and physiological angiogenesis. In this study we investigated its potential role in the regulation of inflammation by testing the response of Endoglin heterozygous (Eng(+/-)) mice to experimental colitis.C57BL/6 Eng(+/-) and littermate control mice drank water supplemented with 3% dextran sulfate sodium (DSS) for 5 days and were monitored for up to 26 days for clinical signs of colitis. Inflammation, crypt damage, and angiogenic index were scored on histological sections of distal c…
Changes in Gastric Mucosal Permeability Induced by Haemorrhagic Shock in the Anaesthetized Rat: - Modulation by Acid
1998
Abstract Gastric mucosal damage induced by haemorrhagic shock in the anaesthetized rat has been evaluated by studying changes in capillary-to-lumen clearance of fluorescein isothiocyanate (FITC)-labelled dextran. Haemorrhagic shock (20 min ischaemia + 20 min reperfusion) induced a significant increase in blood-to-lumen permeability to FITC-dextran of different molecular weight (10 000, 40 000 and 70 000) without modifying the macroscopic integrity of the gastric mucosa. The increase in vascular permeability was dependent on the time of administration of the tracer and was correlated with an elevation of the protein content of the gastric lumen. Intravenous administration of the secretagogue…
Fingolimod (FTY720-P) Does Not Stabilize the Blood–Brain Barrier under Inflammatory Conditions in an in Vitro Model
2015
Breakdown of the blood-brain barrier (BBB) is an early hallmark of multiple sclerosis (MS), a progressive inflammatory disease of the central nervous system. Cell adhesion in the BBB is modulated by sphingosine-1-phosphate (S1P), a signaling protein, via S1P receptors (S1P\(_1\)). Fingolimod phosphate (FTY720-P) a functional S1P\(_1\) antagonist has been shown to improve the relapse rate in relapsing-remitting MS by preventing the egress of lymphocytes from lymph nodes. However, its role in modulating BBB permeabilityin particular, on the tight junction proteins occludin, claudin 5 and ZO-1has not been well elucidated to date. In the present study, FTY720-P did not change the transendotheli…
Computer simulation of oxygen tension histograms--a possibility for interpretation of microelectrode measurements.
1972
Mit Sauerstoff-Mikroelektroden werden die lokalen Werte des Sauerstoffpartialdruckes im Mikrobereich der Organe gemessen und graphisch als Haufigkeitsverteilungen (Histogramme) dargestellt. Theoretisch wird der Einfluss der Kapillaranordnung (Gleich-, Gegenstromsystem und Kapillarnetzwerk) auf die Haufigkeitsverteilung der P02 Werte untersucht. Die fur zweidimensionale Modelle durchgefuhrte Analyse zeigt, dass Unterschiede in der Durchblutung, wie sie in den einzelnen Zweigen der Kapillarnetzwerke auftreten, einen starken Einfluss auf die Histogramme haben.
Image-Guided Synthesis Reveals Potent Blood-Brain Barrier Permeable Histone Deacetylase Inhibitors
2014
Recent studies have revealed that several histone deacetylase (HDAC) inhibitors, which are used to study/treat brain diseases, show low blood-brain barrier (BBB) penetration. In addition to low HDAC potency and selectivity observed, poor brain penetrance may account for the high doses needed to achieve therapeutic efficacy. Here we report the development and evaluation of highly potent and blood-brain barrier permeable HDAC inhibitors for CNS applications based on an image-guided approach involving the parallel synthesis and radiolabeling of a series of compounds based on the benzamide HDAC inhibitor, MS-275 as a template. BBB penetration was optimized by rapid carbon-11 labeling and PET im…
Anti-inflammatory glycoterpenoids from Scrophularia auriculata.
2000
The activity of the four glycoterpenoids: two saponins, verbascosaponin A and verbascosaponin, and two iridoids, scropolioside A and scrovalentinoside, isolated from Scrophularia auriculata ssp. pseudoauriculata, were studied in different models of acute and chronic inflammation. Both saponins significantly inhibited the mouse paw edema induced by carrageenan and ear edema induced by single and multiple doses of 12-O-tetradecanoylphorbol 13-acetate (TPA). Verbascosaponin A showed a potency twice as high as that of indomethacin in the acute TPA model. Verbascosaponin A and scropolioside A were active after a long latency period against ethyl phenylpropiolate edema, as are glucocorticoids. Wh…
Permeability properties of a three-cell type in vitro model of blood-brain barrier.
2005
We previously found that RBE4.B brain capillary endothelial cells (BCECs) form a layer with blood‐brain barrier (BBB) properties if co‐cultured with neurons for at least one week. As astrocytes are known to modulate BBB functions, we further set a culture system that included RBE4.B BCECs, neurons and astrocytes. In order to test formation of BBB, we measured the amount of (3)H‐sucrose able to cross the BCEC layer in this three‐cell type model of BBB. Herein we report that both neurons and astrocytes induce a decrease in the permeability of the BCEC layer to sucrose. These effects are synergic as if BCECs are cultured with both neurons and astrocytes for 5 days, permeability to sucrose decr…
Caspase-3 contributes to ZO-1 and Cl-5 tight-junction disruption in rapid anoxic neurovascular unit damage.
2011
BACKGROUND: Tight-junction (TJ) protein degradation is a decisive step in hypoxic blood-brain barrier (BBB) breakdown in stroke. In this study we elucidated the impact of acute cerebral ischemia on TJ protein arrangement and the role of the apoptotic effector protease caspase-3 in this context. METHODOLOGY/PRINCIPAL FINDINGS: We used an in vitro model of the neurovascular unit and the guinea pig whole brain preparation to analyze with immunohistochemical methods the BBB properties and neurovascular integrity. In both methodological approaches we observed rapid TJ protein disruptions after 30 min of oxygen and glucose deprivation or middle cerebral artery occlusion, which were accompanied by…
Vascular Endothelial Growth Factor, a Key Modulator of the Anti-Tumor Immune Response
2021
During tumor growth, angiogenesis is required to ensure oxygen and nutrient transport to the tumor. Vascular endothelial growth factor (VEGF) is the major inducer of angiogenesis and appears to be a key modulator of the anti-tumor immune response. Indeed, VEGF modulates innate and adaptive immune responses through direct interactions and indirectly by modulating protein expressions on endothelial cells or vascular permeability. The inhibition of the VEGF signaling pathway is clinically approved for the treatment of several cancers. Therapies targeting VEGF can modulate the tumor vasculature and the immune response. In this review, we discuss the roles of VEGF in the anti-tumor immune respon…
The impact of the receptor binding profiles of the vascular endothelial growth factors on their angiogenic features
2013
Abstract Background Vascular endothelial growth factors (VEGFs) are potential therapeutic agents for treatment of ischemic diseases. Their angiogenic effects are mainly mediated through VEGF receptor 2 (VEGFR2). Methods Receptor binding, signaling, and biological efficacy of several VEGFR2 ligands were compared to determine their characteristics regarding angiogenic activity and vascular permeability. Results Tested VEGFR2 ligands induced receptor tyrosine phosphorylation with different efficacy depending on their binding affinities. However, the tyrosine phosphorylation pattern and the activation of the major downstream signaling pathways were comparable. The maximal angiogenic effect stim…