DCE-MRI of Brain Fluid Barriers: In Vivo Water Cycling at the Human Choroid Plexus

Author(s):  
Valerie C. Anderson ◽  
Ian J. Tagge ◽  
Aaron Doud ◽  
Xin Li ◽  
Charles S. Springer ◽  
...  
2020 ◽  
Author(s):  
Mohammed R. Shaker ◽  
Justin Cooper-White ◽  
Ernst J. Wolvetang

ABSTRACTBoth the choroid plexus (CP) and the cortex are derived from the rostral neural tube during early embryonic development. In addition to producing CSF, the CP secretes essential factors that orchestrate cortical development and later neurogenesis. Previous brain modeling efforts with human pluripotent stem cells (hPSCs) generated either cortical or CP tissues in 3D culture. Here, we used hPSC-derived neuroectodermal cells, the building blocks of the anterior body, to simultaneously generate CP that forms ventricles and cortical cells in organoids (CVCOs), which can be maintained as 3D organoid cultures. Large scale culture revealed reproducibility of the protocol independent of cell lines, clones or batches. CVCOs contain mature and functional CP that projects multiple cilia into the ventricle-like fluid filled cysts and is in direct contact with appropriately patterned cortical cells. CVCOs thus recapitulate key features of developing forebrain structures observed in in vivo and constitute a useful for dissecting the role of CP in human forebrain development in health and disease.


1976 ◽  
Vol 230 (4) ◽  
pp. 1101-1107 ◽  
Author(s):  
R Spector

Total thiamine (free thiamine and thiamine phosphates) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the CSF was measured in rabbits. In vivo, total thiamine transport into CSF, choroid plexus, and brain was saturable. At the normal plasma total thiamine concentration, less than 5% of total thiamine entry into CSF, choroid plexus, and brain was by simple diffusion. The relative turnovers of total thiamine in choroid plexus, whole brain, and CSF were 5, 2, and 14% per h, respectively, when measured by the penetration of 35S-labeled thiamine injected into blood. From the CSF, clearance of [35S]thiamine relative to mannitol was not saturable after the intraventricular injection of various concentrations of thiamine. However, a portion of the [35S]thiamine cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [35S]thiamine against a concentration gradient by an active saturable process that did not depend on pyrophosphorylation of the [35S]thiamine. The [35S]thiamine accumulated within the choroid plexus in vitro was readily released. These results were interpreted as showing that the entry of total thiamine into the brain and CSF from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus.


Author(s):  
L. A. R. Righesso ◽  
M. Terekhov ◽  
H. Götz ◽  
M. Ackermann ◽  
T. Emrich ◽  
...  

Abstract Objectives Micro-computed tomography (μ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monitoring neovascularization during bone regeneration. Additionally, the suitability of blood perfusion as a surrogate of the efficacy of osteoplastic materials was evaluated. Materials and methods Sixteen rabbits were used and equally divided into four groups, according to the time of euthanasia (2, 3, 4, and 6 weeks after surgery). The animals were submitted to two 8-mm craniotomies that were filled with blood or autogenous bone. Neovascularization was assessed in vivo through DCE-MRI, and bone regeneration, ex vivo, through μ-CT and histology. Results The defects could be consistently identified, and their blood perfusion measured through DCE-MRI, there being statistically significant differences within the blood clot group between 3 and 6 weeks (p = 0.029), and between the former and autogenous bone at six weeks (p = 0.017). Nonetheless, no significant correlations between DCE-MRI findings on neovascularization and μ-CT (r =−0.101, 95% CI [−0.445; 0.268]) or histology (r = 0.305, 95% CI [−0.133; 0.644]) findings on bone regeneration were observed. Conclusions These results support the hypothesis that DCE-MRI can be used to monitor neovascularization but contradict the premise that it could predict bone regeneration as well.


2009 ◽  
Vol 22 (10) ◽  
pp. 1036-1046 ◽  
Author(s):  
Mariacristina Valerio ◽  
Valeria Panebianco ◽  
Alessandro Sciarra ◽  
Marcello Osimani ◽  
Stefano Salsiccia ◽  
...  

2019 ◽  
Vol 13 ◽  
Author(s):  
Monica Van Den Berg ◽  
Aneta Keliris ◽  
Inès Ben-Nejma ◽  
Marleen Verhoye ◽  
Georgios Keliris ◽  
...  

Author(s):  
Alexa N. Lauer ◽  
Rene Scholtysik ◽  
Andreas Beineke ◽  
Christoph Georg Baums ◽  
Kristin Klose ◽  
...  

Streptococcus suis (S. suis) is an important opportunistic pathogen, which can cause septicemia and meningitis in pigs and humans. Previous in vivo observations in S. suis-infected pigs revealed lesions at the choroid plexus (CP). In vitro experiments with primary porcine CP epithelial cells (PCPEC) and human CP epithelial papilloma (HIBCPP) cells demonstrated that S. suis can invade and traverse the CP epithelium, and that the CP contributes to the inflammatory response via cytokine expression. Here, next generation sequencing (RNA-seq) was used to compare global transcriptome profiles of PCPEC and HIBCPP cells challenged with S. suis serotype (ST) 2 infected in vitro, and of pigs infected in vivo. Identified differentially expressed genes (DEGs) were, amongst others, involved in inflammatory responses and hypoxia. The RNA-seq data were validated via quantitative PCR of selected DEGs. Employing Gene Set Enrichment Analysis (GSEA), 18, 28, and 21 enriched hallmark gene sets (GSs) were identified for infected HIBCPP cells, PCPEC, and in the CP of pigs suffering from S. suis ST2 meningitis, respectively, of which eight GSs overlapped between the three different sample sets. The majority of these GSs are involved in cellular signaling and pathways, immune response, and development, including inflammatory response and hypoxia. In contrast, suppressed GSs observed during in vitro and in vivo S. suis ST2 infections included those, which were involved in cellular proliferation and metabolic processes. This study suggests that similar cellular processes occur in infected human and porcine CP epithelial cells, especially in terms of inflammatory response.


2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv9-iv10
Author(s):  
Ashirwad Merve ◽  
Xinyu Zhang ◽  
Nicola Pomella ◽  
Serena Acquati ◽  
Joerg Hoeck ◽  
...  

Abstract Choroid plexus tumours (CPT) account for up to 20% of brain tumours in children under 2 years of age. Histologically CPTs are classified into three categories - Choroid Plexus Papilloma (CPP), Atypical Choroid Plexus Papilloma (ACPP) and Choroid Plexus Carcinoma (CPC). Recent literature demonstrates that CPP and ACPP are molecularly distinct from CPC. Initial management for CPT include surgery followed by adjuvant therapy in selected patients. Currently there are no disease-specific chemotherapeutic agents available, possibly because of their rarity and paucity of faithful pre-clinical experimental models. In this study we show that c-Myc overexpression in the choroid plexus epithelium induces T-cell inflammation-dependent choroid plexus papillomas in a mouse model. We demonstrate that c-MYC is expressed in a substantial proportion of human choroid plexus tumours and that this subgroup of tumours is characterised by an inflammatory transcriptome and significant inflammatory infiltrates. We observed that triple transgenic compound mutant mouse model with c-Myc overexpression in an immune-suppressed background led to a decreased incidence of CPP and reduced tumour bulk. A reduced tumour size was also observed when c-Myc overexpressing mice were treated with anti-CD3 antibodies. Our data raise the possibility that benign choroid plexus tumours expressing c-MYC could be amenable to medical therapy with anti-inflammatory drugs.


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