scholarly journals miR-98 and let-7g* Protect the Blood-Brain Barrier Under Neuroinflammatory Conditions

2015 ◽  
Vol 35 (12) ◽  
pp. 1957-1965 ◽  
Author(s):  
Slava Rom ◽  
Holly Dykstra ◽  
Viviana Zuluaga-Ramirez ◽  
Nancy L Reichenbach ◽  
Yuri Persidsky
Keyword(s):  
Blood Brain Barrier ◽  
Glycogen Synthase ◽  
Leukocyte Adhesion ◽  
Brain Barrier ◽  
Brain Endothelium ◽  
In Vivo Models ◽  
Blood Brain ◽  
Microarray Screening

Pathologic conditions in the central nervous system, regardless of the underlying injury mechanism, show a certain level of blood-brain barrier (BBB) impairment. Endothelial dysfunction is the earliest event in the initiation of vascular damage caused by inflammation due to stroke, atherosclerosis, trauma, or brain infections. Recently, microRNAs (miRNAs) have emerged as a class of gene expression regulators. The relationship between neuroinflammation and miRNA expression in brain endothelium remains unexplored. Previously, we showed the BBB-protective and anti-inflammatory effects of glycogen synthase kinase (GSK) 3β inhibition in brain endothelium in in vitro and in vivo models of neuroinflammation. Using microarray screening, we identified miRNAs induced in primary human brain microvascular endothelial cells after exposure to the pro-inflammatory cytokine, tumor necrosis factor-α, with/out GSK3β inhibition. Among the highly modified miRNAs, let-7 and miR-98 were predicted to target the inflammatory molecules, CCL2 and CCL5. Overexpression of let-7 and miR-98 in vitro and in vivo resulted in reduced leukocyte adhesion to and migration across endothelium, diminished expression of pro-inflammatory cytokines, and increased BBB tightness, attenuating barrier ‘leakiness’ in neuroinflammation conditions. For the first time, we showed that miRNAs could be used as a therapeutic tool to prevent the BBB dysfunction in neuroinflammation.

Drug Transfer Across the Blood-Brain Barrier: Correlation Between in Vitro and in Vivo Models

1993 ◽  
pp. 161-161
Author(s):  
M. P. Dehouck ◽  
B. Dehouck ◽  
J. C. Fruchart ◽  
R. Cecchelli ◽  
P. Jolliet-Riant ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
In Vivo Models ◽  
Drug Transfer ◽  
Blood Brain

Drug transport to the brain: comparison between in vitro and in vivo models of the blood-brain barrier

1995 ◽  
Vol 3 (6) ◽  
pp. 357-365 ◽  
Author(s):  
M.P. Dehouck ◽  
B. Dehouck ◽  
C. Schluep ◽  
M. Lemaire ◽  
R. Cecchelli
Keyword(s):  
Blood Brain Barrier ◽  
Drug Transport ◽  
Brain Barrier ◽  
In Vivo Models ◽  
Blood Brain ◽  
The Brain

Drug Transfer Across the Blood-Brain Barrier: Correlation Between In Vitro and In Vivo Models

1992 ◽  
Vol 58 (5) ◽  
pp. 1790-1797 ◽  
Author(s):  
Marie-Pierre Dehouck ◽  
Pascale Jolliet-Riant ◽  
Françoise Brée ◽  
Jean-Charles Fruchart ◽  
Roméo Cecchelli ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
In Vivo Models ◽  
Drug Transfer ◽  
Blood Brain

scholarly journals Mucosal and blood-brain barrier transport kinetics of the plant N-alkylamide spilanthol using in vitro and in vivo models

2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Lieselotte Veryser ◽  
Lien Taevernier ◽  
Tanmayee Joshi ◽  
Pratima Tatke ◽  
Evelien Wynendaele ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Transport Kinetics ◽  
Brain Barrier ◽  
In Vivo Models ◽  
Blood Brain ◽  
Kinetics Of

scholarly journals miR-98 reduces endothelial dysfunction by protecting blood–brain barrier (BBB) and improves neurological outcomes in mouse ischemia/reperfusion stroke model

2019 ◽  
Vol 40 (10) ◽  
pp. 1953-1965 ◽  
Author(s):  
David L Bernstein ◽  
Viviana Zuluaga-Ramirez ◽  
Sachin Gajghate ◽  
Nancy L Reichenbach ◽  
Boris Polyak ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Brain Barrier ◽  
Inflammatory Factors ◽  
Brain Endothelium ◽  
Blood Brain ◽  
The Brain

Most neurological diseases, including stroke, lead to some degree of blood–brain barrier (BBB) dysfunction. A significant portion of BBB injury is caused by inflammation, due to pro-inflammatory factors produced in the brain, and by leukocyte engagement of the brain endothelium. Recently, microRNAs (miRNAs) have appeared as major regulators of inflammation-induced changes to gene expression in the microvascular endothelial cells (BMVEC) that comprise the BBB. However, miRNAs’ role during cerebral ischemia/reperfusion is still underexplored. Endothelial levels of miR-98 were significantly altered following ischemia/reperfusion insults, both in vivo and in vitro, transient middle cerebral artery occlusion (tMCAO), and oxygen–glucose deprivation (OGD), respectively. Overexpression of miR-98 reduced the mouse’s infarct size after tMCAO. Further, miR-98 lessened infiltration of proinflammatory Ly6CHI leukocytes into the brain following stroke and diminished the prevalence of M1 (activated) microglia within the impacted area. miR-98 attenuated BBB permeability, as demonstrated by changes to fluorescently-labeled dextran penetration in vivo and improved transendothelial electrical resistance (TEER) in vitro. Treatment with miR-98 improved significantly the locomotor impairment. Our study provides identification and functional assessment of miRNAs in brain endothelium and lays the groundwork for improving therapeutic approaches for patients suffering from ischemic attacks.

Activation of PKC modulates blood-brain barrier endothelial cell permeability changes induced by hypoxia and posthypoxic reoxygenation

2005 ◽  
Vol 289 (5) ◽  
pp. H2012-H2019 ◽  
Author(s):  
Melissa A. Fleegal ◽  
Sharon Hom ◽  
Lindsay K. Borg ◽  
Thomas P. Davis
Keyword(s):  
Blood Brain Barrier ◽  
Paracellular Permeability ◽  
Cell Permeability ◽  
Brain Barrier ◽  
Cerebral Microvessels ◽  
Permeability Changes ◽  
Blood Brain ◽  
Brain Microvessel

The blood-brain barrier (BBB) is a metabolic and physiological barrier important for maintaining brain homeostasis. The aim of this study was to determine the role of PKC activation in BBB paracellular permeability changes induced by hypoxia and posthypoxic reoxygenation using in vitro and in vivo BBB models. In rat brain microvessel endothelial cells (RMECs) exposed to hypoxia (1% O2-99% N2; 24 h), a significant increase in total PKC activity was observed, and this was reduced by posthypoxic reoxygenation (95% room air-5% CO2) for 2 h. The expression of PKC-βII, PKC-γ, PKC-η, PKC-μ, and PKC-λ also increased following hypoxia (1% O2-99% N2; 24 h), and these protein levels remained elevated following posthypoxic reoxygenation (95% room air-5% CO2; 2 h). Increases in the expression of PKC-ε and PKC-ζ were also observed following posthypoxic reoxygenation (95% room air-5% CO2; 2 h). Moreover, inhibition of PKC with chelerythrine chloride (10 μM) attenuated the hypoxia-induced increases in [14C]sucrose permeability. Similar to what was observed in RMECs, total PKC activity was also stimulated in cerebral microvessels isolated from rats exposed to hypoxia (6% O2-94% N2; 1 h) and posthypoxic reoxygenation (room air; 10 min). In contrast, hypoxia (6% O2-94% N2; 1 h) and posthypoxic reoxygenation (room air; 10 min) significantly increased the expression levels of only PKC-γ and PKC-θ in the in vivo hypoxia model. These data demonstrate that hypoxia-induced BBB paracellular permeability changes occur via a PKC-dependent mechanism, possibly by differentially regulating the protein expression of the 11 PKC isozymes.

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