scholarly journals Poly(ADP-ribose) Polymerase-1 Inhibition in Brain Endothelium Protects the Blood—Brain Barrier under Physiologic and Neuroinflammatory Conditions

2014 ◽  
Vol 35 (1) ◽  
pp. 28-36 ◽  
Author(s):  
Slava Rom ◽  
Viviana Zuluaga-Ramirez ◽  
Holly Dykstra ◽  
Nancy L Reichenbach ◽  
Servio H Ramirez ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Parp Inhibition ◽  
Inflammatory Factors ◽  
In Vivo Model ◽  
Brain Endothelium ◽  
Monocyte Migration ◽  
Blood Brain ◽  
And Migration

Blood—brain barrier (BBB) dysfunction seen in neuroinflammation contributes to mortality and morbidity in multiple sclerosis, encephalitis, traumatic brain injury, and stroke. Identification of molecular targets maintaining barrier function is of clinical relevance. We used a novel in vivo model of localized aseptic meningitis where tumor necrosis factor alpha (TNFα) was introduced intracerebrally and surveyed cerebral vascular changes and leukocyte—endothelium interactions by intravital videomicroscopy. Poly(ADP-ribose) polymerase-1 (PARP) inhibition significantly reduced leukocyte adhesion to and migration across brain endothelium in cortical microvessels. PARP inactivation diminished BBB permeability in an in vivo model of systemic inflammation. PARP suppression in primary human brain microvascular endothelial cells (BMVEC), an in vitro model of BBB, enhanced barrier integrity and augmented expression of tight junction proteins. PARP inhibition in BMVEC diminished human monocyte adhesion to TNFα-activated BMVEC (up to 65%) and migration (80–100%) across BBB models. PARP suppression decreased expression of adhesion molecules and decreased activity of GTPases (controlling BBB integrity and monocyte migration across the BBB). PARP inhibitors down-regulated expression of inflammatory genes and dampened secretion of pro-inflammatory factors increased by TNFα in BMVEC. These results point to PARP suppression as a novel approach to BBB protection in the setting of endothelial dysfunction caused by inflammation.

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.

The pecten oculi of the chicken as a new in vivo model of the blood-brain barrier

1996 ◽  
Vol 285 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Holger Gerhardt ◽  
Stefan Liebner ◽  
Hartwig Wolburg
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
In Vivo Model ◽  
Blood Brain ◽  
Pecten Oculi

scholarly journals The Capsule Supports Survival but Not Traversal ofEscherichia coli K1 across the Blood-Brain Barrier

1999 ◽  
Vol 67 (7) ◽  
pp. 3566-3570 ◽  
Author(s):  
Jill A. Hoffman ◽  
Carol Wass ◽  
Monique F. Stins ◽  
Kwang Sik Kim
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
In Vivo Model ◽  
E Coli ◽  
Blood Brain ◽  
Vitro Model ◽  
K1 Capsule

ABSTRACT The vast majority of cases of gram-negative meningitis in neonates are caused by K1-encapsulated Escherichia coli. The role of the K1 capsule in the pathogenesis of E. coli meningitis was examined with an in vivo model of experimental hematogenousE. coli K1 meningitis and an in vitro model of the blood-brain barrier. Bacteremia was induced in neonatal rats with theE. coli K1 strain C5 (O18:K1) or its K1−derivative, C5ME. Subsequently, blood and cerebrospinal fluid (CSF) were obtained for culture. Viable bacteria were recovered from the CSF of animals infected with E. coli K1 strains only; none of the animals infected with K1− strains had positive CSF cultures. However, despite the fact that their cultures were sterile, the presence of O18 E. coli was demonstrated immunocytochemically in the brains of animals infected with K1− strains and was seen by staining of CSF samples. In vitro, brain microvascular endothelial cells (BMEC) were incubated with K1+ and K1− E. coli strains. The recovery of viable intracellular organisms of the K1+strain was significantly higher than that for the K1−strain (P = 0.0005). The recovery of viable intracellular K1− E. coli bacteria was increased by cycloheximide treatment of BMEC (P = 0.0059) but was not affected by nitric oxide synthase inhibitors or oxygen radical scavengers. We conclude that the K1 capsule is not necessary for the invasion of bacteria into brain endothelial cells but is responsible for helping to maintain bacterial viability during invasion of the blood-brain barrier.

scholarly journals SARS-CoV-2 crosses the blood–brain barrier accompanied with basement membrane disruption without tight junctions alteration

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ling Zhang ◽  
Li Zhou ◽  
Linlin Bao ◽  
Jiangning Liu ◽  
Hua Zhu ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Inflammatory Responses ◽  
Vascular Wall ◽  
Brain Barrier ◽  
Inflammatory Factors ◽  
Blood Brain

AbstractSARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals. However, it remains unclear whether and how SARS-CoV-2 crosses the blood–brain barrier (BBB). Herein, SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space, as well as in brain microvascular endothelial cells (BMECs) in the infected K18-hACE2 transgenic mice. Moreover, the permeability of the infected vessel was increased. Furthermore, disintegrity of BBB was discovered in the infected hamsters by administration of Evans blue. Interestingly, the expression of claudin5, ZO-1, occludin and the ultrastructure of tight junctions (TJs) showed unchanged, whereas, the basement membrane was disrupted in the infected animals. Using an in vitro BBB model that comprises primary BMECs with astrocytes, SARS-CoV-2 was found to infect and cross through the BMECs. Consistent with in vivo experiments, the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs. Besides, inflammatory responses including vasculitis, glial activation, and upregulated inflammatory factors occurred after SARS-CoV-2 infection. Overall, our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.

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.

Noninvasive Characterization of Human Glymphatics and Meningeal Lymphatics in an in vivo Model of Blood–Brain Barrier Leakage

2020 ◽  
Vol 89 (1) ◽  
pp. 111-124
Author(s):  
Chia‐Hung Wu ◽  
Jiing‐Feng Lirng ◽  
Yu‐Hsiang Ling ◽  
Yen‐Feng Wang ◽  
Hsiu‐Mei Wu ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
In Vivo Model ◽  
Blood Brain ◽  
Noninvasive Characterization

scholarly journals Impact of Curcuma longa extract on the expression level of brain transporters in in vivo model

2019 ◽  
Vol 65 (1) ◽  
pp. 32-39
Author(s):  
Marta Bukowska ◽  
Anna Bogacz ◽  
Marlena Wolek ◽  
Przemysław Ł. Mikołajczak ◽  
Piotr Olbromski ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Curcuma Longa ◽  
Mrna Level ◽  
Expression Level ◽  
Brain Barrier ◽  
In Vivo Model ◽  
Toxic Substances ◽  
Blood Brain ◽  
The Brain

Summary Introduction: Blood brain barrier and multidrug resistance phenomenon are subjects of many investigations. Mainly, because of their functions in protecting the central nervous system (CNS) by blocking the delivery of toxic substances to the brain. This special function has some disadvantages, like drug delivery to the brain in neurodegenerative diseases Objective: The aim of this study was to examine how natural and synthetic substances affect the expression levels of genes (Mdr1a, Mdr1b, Mrp1, Mrp2, Oatp1a4, Oatp1a5 and Oatp1c1) that encode transporters in the blood-brain barrier. Methods: cDNA was synthesized from total RNA isolated from rat hippocampus. The expression level of genes was determined using real-time PCR (RT-PCR) method. Results: Our findings showed that verapamil, as a synthetic substance, caused the greatest reduction of mRNA level of genes studied. The standardized extract of Curcuma longa reduced the expression level for Mrp1 and Mrp2, whereas the increase of mRNA level was observed for Mdr1b, Oatp1a5 and Oatp1c1. Conclusions: These results suggests that herbal extracts may play an important role in overcoming the blood brain barrier during pharmacotherapy.

Novel in vivo model of the human blood-brain barrier

1998 ◽  
Vol 90 (1) ◽  
pp. 20
Author(s):  
L.M. Dallasta ◽  
J.L. Maguire ◽  
M.G. White ◽  
A.P. Mehta ◽  
C.A. Wiley ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Human Blood ◽  
Brain Barrier ◽  
In Vivo Model ◽  
Blood Brain
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