scholarly journals Glucocorticoid effects on endothelial barrier function in the murine brain endothelial cell line cEND incubated with sera from patients with multiple sclerosis

2010 ◽  
Vol 16 (3) ◽  
pp. 293-302 ◽  
Author(s):  
Kinga G Blecharz ◽  
Aiden Haghikia ◽  
Mariusz Stasiolek ◽  
Niels Kruse ◽  
Detlev Drenckhahn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Endothelial Cell ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Junction Protein ◽  
Blood Brain Barrier Integrity

Compromised blood—brain barrier integrity is a major hallmark of active multiple sclerosis (MS). Alterations in brain endothelial tight junction protein and gene expression occur early during neuroinflammation but there is little known about the underlying mechanisms. In this study, we analysed barrier compromising effects of sera from MS patients and barrier restoring effects of glucocorticoids on blood—brain barrier integrity in vitro. cEND murine brain microvascular endothelial cell monolayers were incubated with sera from patients in active phase of disease or in relapse. Data were compared with effects of the glucocorticoid dexamethasone alone or in combination with MS sera on barrier integrity. Tight junction protein levels and gene expression were evaluated concomitant with barrier integrity. We reveal downregulation of claudin-5 and occludin protein and mRNA and an accompanying upregulation in expression of matrix metalloproteinase MMP-9 after incubation with serum from active disease and remission and also a minor reconstitution of barrier functions related to dexamethasone treatment. Moreover, we for the first time describe downregulation of claudin-5 and occludin protein after incubation of cEND cells with sera from patients in remission phase of MS. Our findings reveal direct and differential effects of MS sera on blood-brain barrier integrity.

Abstract TP256: Mouse Model of Uremic Cerebral Microbleeds

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Wei Ling Lau ◽  
Mary Tarbiat-Boldaji ◽  
Hayley Smalls ◽  
Ane Nunes ◽  
Javad Savoj ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Cerebral Microbleeds ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Increased Risk ◽  
Junction Protein ◽  
Blood Brain Barrier Integrity

Introduction: Cerebral microbleeds are more common in chronic kidney disease (CKD) and dialysis patients compared to the general population. Diminished kidney function alone appears to be a risk factor for microbleeds, independent of age and hypertension. Microbleed burden in CKD patients is associated with increased risk of future hemorrhagic stroke and with cognitive dysfunction. The mechanisms that drive uremic microbleed formation are unclear. Hypothesis: We hypothesized that CKD mice are predisposed to develop cerebral microhemorrhages (the pathologic substrate of microbleeds), and that a standardized inflammatory stimulus (lipopolysaccharide, LPS) will amplify microhemorrhage burden in CKD mice compared to non-CKD controls (CTL). We also hypothesized that uremia induces depletion of tight junction proteins, altering blood-brain barrier integrity and representing a potential mechanism of microbleed formation. Methods: Animal groups included CTL (n=3), CKD (n=3), CTL+LPS (n=5) and CKD+LPS (n=5). CKD induction in male C57BL/6 mice was achieved via nephrotoxic adenine diet x18 days. Two weeks following CKD induction, CKD and control mice were treated with LPS 1 mg/kg i.p. dosed at 0, 6 and 24 hours. Brains were harvested one week after LPS injections and 40-micron sections were stained using Prussian blue to identify microhemorrhages. Immunohistochemistry was performed for the blood-brain barrier tight junction protein claudin-5. Results: CKD mice had significantly elevated blood urea nitrogen, and tubulointerstitial fibrosis was present on kidney histology. Total number of microhemorrhages per brain was 2.3±1.5 (mean ± standard error of the mean) for CTL mice, 8.3±1.5 for CKD mice, 23.2±4.2 for CTL+LPS mice, and 27.6±6.2 for CKD+LPS mice (p<0.05 for CKD+LPS vs. CTL). Immunostaining showed decreased claudin-5 expression in CKD mice compared to CTL. Conclusions: We have generated a mouse model that will facilitate future mechanistic studies in the field of uremic microbleeds. Our initial findings suggest that CKD alters blood-brain barrier integrity and that inflammation amplifies development of microbleeds in CKD.

scholarly journals Interleukin-34 Restores Blood–Brain Barrier Integrity by Upregulating Tight Junction Proteins in Endothelial Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e115981 ◽  
Author(s):  
Shijie Jin ◽  
Yoshifumi Sonobe ◽  
Jun Kawanokuchi ◽  
Hiroshi Horiuchi ◽  
Yi Cheng ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Tight Junction Proteins ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity ◽  
Junction Proteins

scholarly journals Scan-stratified case-control sampling for modeling blood-brain barrier integrity in multiple sclerosis

2015 ◽  
Vol 34 (20) ◽  
pp. 2872-2880 ◽  
Author(s):  
Gina-Maria Pomann ◽  
Elizabeth M. Sweeney ◽  
Daniel S. Reich ◽  
Ana-Maria Staicu ◽  
Russell T. Shinohara
Keyword(s):  
Multiple Sclerosis ◽  
Blood Brain Barrier ◽  
Case Control ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

scholarly journals Effect of heat stress on blood-brain barrier integrity in iPS cell-derived microvascular endothelial cell models

PLoS ONE ◽  
2019 ◽  
Vol 14 (9) ◽  
pp. e0222113 ◽  
Author(s):  
Tomoko Yamaguchi ◽  
Kentaro Shimizu ◽  
Yasuhiro Kokubu ◽  
Misae Nishijima ◽  
Shuko Takeda ◽  
...  
Keyword(s):  
Heat Stress ◽  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Microvascular Endothelial Cell ◽  
Cell Models ◽  
Ips Cell ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

scholarly journals Mice deficient in endothelial α5 integrin are profoundly resistant to experimental ischemic stroke

2016 ◽  
Vol 37 (1) ◽  
pp. 85-96 ◽  
Author(s):  
Jill Roberts ◽  
Leon de Hoog ◽  
Gregory J Bix
Keyword(s):  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Infarct Volume ◽  
Ischemic Injury ◽  
Glucose Deprivation ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

Stroke is a disease in dire need of better therapies. We have previously shown that a fragment of the extracellular matrix proteoglycan, perlecan, has beneficial effects following cerebral ischemia via the α5β1 integrin receptor. We now report that endothelial cell selective α5 integrin deficient mice (α5 KO) are profoundly resistant to ischemic infarct after transient middle cerebral artery occlusion. Specifically, α5 KOs had little to no infarct 2–3 days post-stroke, whereas controls had an increase in mean infarct volume over the same time period as expected. Functional outcome is also improved in the α5 KOs compared with controls. Importantly, no differences in cerebrovascular anatomy or collateral blood flow were noted that could account for this difference in ischemic injury. Rather, we demonstrate that α5 KOs have increased blood-brain barrier integrity (increased expression of claudin-5, and absent brain parenchymal IgG extravasation) after stroke compared with controls, which could explain their resistance to ischemic injury. Additionally, inhibition of α5 integrin in vitro leads to decreased permeability of brain endothelial cells following oxygen-glucose deprivation. Together, these findings indicate endothelial cell α5 integrin plays an important role in stroke outcome and blood-brain barrier integrity, suggesting that α5 integrin could be a novel therapeutic target for stroke.

scholarly journals Multimodal investigations of trans-endothelial cell trafficking under condition of disrupted blood-brain barrier integrity

2010 ◽  
Vol 11 (1) ◽  
pp. 34 ◽  
Author(s):  
Nicola Marchi ◽  
Qingshan Teng ◽  
Minh T Nguyen ◽  
Linda Franic ◽  
Nirav K Desai ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Cell Trafficking ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity
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