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 ◽  
...  
1996 ◽  
Vol 285 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Holger Gerhardt ◽  
Stefan Liebner ◽  
Hartwig Wolburg

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Annarita Falanga ◽  
Giuseppina Iachetta ◽  
Lucia Lombardi ◽  
Emiliana Perillo ◽  
Assunta Lombardi ◽  
...  

1999 ◽  
Vol 67 (7) ◽  
pp. 3566-3570 ◽  
Author(s):  
Jill A. Hoffman ◽  
Carol Wass ◽  
Monique F. Stins ◽  
Kwang Sik Kim

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.


2014 ◽  
Vol 35 (1) ◽  
pp. 28-36 ◽  
Author(s):  
Slava Rom ◽  
Viviana Zuluaga-Ramirez ◽  
Holly Dykstra ◽  
Nancy L Reichenbach ◽  
Servio H Ramirez ◽  
...  

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.


1998 ◽  
Vol 90 (1) ◽  
pp. 20
Author(s):  
L.M. Dallasta ◽  
J.L. Maguire ◽  
M.G. White ◽  
A.P. Mehta ◽  
C.A. Wiley ◽  
...  

2019 ◽  
Vol 65 (1) ◽  
pp. 32-39
Author(s):  
Marta Bukowska ◽  
Anna Bogacz ◽  
Marlena Wolek ◽  
Przemysław Ł. Mikołajczak ◽  
Piotr Olbromski ◽  
...  

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.


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