scholarly journals Polar Infection of Echovirus-30 Causes Differential Barrier Affection and Gene Regulation at the Blood–Cerebrospinal Fluid Barrier

2020 ◽  
Vol 21 (17) ◽  
pp. 6268 ◽  
Author(s):  
Marie Wiatr ◽  
Ricardo Figueiredo ◽  
Carolin Stump-Guthier ◽  
Peter Winter ◽  
Hiroshi Ishikawa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Expression Profiles ◽  
Choroid Plexus Papilloma ◽  
Gene Expression Profiles ◽  
Barrier Properties ◽  
Echovirus 30 ◽  
Apical Side

Echovirus-30 (E-30) is responsible for the extensive global outbreaks of meningitis in children. To gain access to the central nervous system, E-30 first has to cross the epithelial blood–cerebrospinal fluid barrier. Several meningitis causing bacteria preferentially infect human choroid plexus papilloma (HIBCPP) cells in a polar fashion from the basolateral cell side. Here, we investigated the polar infection of HIBCPP cells with E-30. Both apical and basolateral infections caused a significant decrease in the transepithelial electrical resistance of HIBCPP cells. However, to reach the same impact on the barrier properties, the multiplicity of infection of the apical side had to be higher than that of the basolateral infection. Furthermore, the number of infected cells at respective time-points after basolateral infection was significantly higher compared to apical infection. Cytotoxic effects of E-30 on HIBCPP cells during basolateral infection were observed following prolonged infection and appeared more drastically compared to the apical infection. Gene expression profiles determined by massive analysis of cDNA ends revealed distinct regulation of specific genes depending on the side of HIBCPP cells’ infection. Altogether, our data highlights the polar effects of E-30 infection in a human in vitro model of the blood–cerebrospinal fluid barrier leading to central nervous system inflammation.

scholarly journals Single-cell immune repertoire and transcriptome sequencing reveals that clonally expanded and transcriptionally distinct lymphocytes populate the aged central nervous system in mice

2021 ◽  
Vol 288 (1945) ◽  
pp. 20202793
Author(s):  
Alexander Yermanos ◽  
Daniel Neumeier ◽  
Ioana Sandu ◽  
Mariana Borsa ◽  
Ann Cathrin Waindok ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
B Cells ◽  
Single Cell ◽  
Somatic Hypermutation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Receptor ◽  
The Central Nervous System

Neuroinflammation plays a crucial role during ageing and various neurological conditions, including Alzheimer's disease, multiple sclerosis and infection. Technical limitations, however, have prevented an integrative analysis of how lymphocyte immune receptor repertoires and their accompanying transcriptional states change with age in the central nervous system. Here, we leveraged single-cell sequencing to simultaneously profile B cell receptor and T cell receptor repertoires and accompanying gene expression profiles in young and old mouse brains. We observed the presence of clonally expanded B and T cells in the central nervous system of aged male mice. Furthermore, many of these B cells were of the IgM and IgD isotypes, and had low levels of somatic hypermutation. Integrating gene expression information additionally revealed distinct transcriptional profiles of these clonally expanded lymphocytes. Our findings implicate that clonally related T and B cells in the CNS of elderly mice may contribute to neuroinflammation accompanying homeostatic ageing.

Myo-inositol transport in the central nervous system

1975 ◽  
Vol 228 (5) ◽  
pp. 1510-1518 ◽  
Author(s):  
R Spector ◽  
AV Lorenzo
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Choroid Plexus ◽  
Intraventricular Injection ◽  
Affinity Constant ◽  
Rapid Injection ◽  
The Central Nervous System

Free myo-inositol (inositol) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the cerebrospinal fluid was measured in rabbits. In vivo, inositol transport from blood into choroid plexus, CSF, and brain was saturable with an apparent affinity constant (K-t) of approximately 0.1 mM. The relative turnover of free inositol in choroid plexus (16 percent/h) was higher than in CSF 4percent/h) and brain (0.3percent/h) when meausred by tissue penetration of tracer [3-H]-labeled inositol injected into blood. However, the passage of tracer inositol was not greater than the passage of mannitol into brain when measured 15 s after a rapid injection of inositol and mannitol into the left common carotid artery. From the CSF, the clearance of inositol relative to inulin was saturable after the intraventricular injection of various concentrations of inositol and inulin. Moreover, a portion of the inositol cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [3-H-labeled myo-inositol against a concentration gradient by a specific, active, saturable process with a K-t of 0.2 mM inositol. These results were interpreted as showing that the entry of inositol into the central nervous system from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus.

Dasatinib Cerebrospinal Fluid Concentration and Plasma Pharmacokinetics: Potential for Central Nervous System Prophylaxis In Philadelphia Chromosome-Positive Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1807-1807
Author(s):  
Naoto Takahashi ◽  
Masatomo Miura ◽  
Stuart Scott ◽  
Hirobumi Saitoh ◽  
Mutsuhito Motegi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Conflicts Of Interest ◽  
Philadelphia Chromosome ◽  
T Test ◽  
Lymphoid Leukemia ◽  
Csf Levels ◽  
Philadelphia Chromosome Positive

Abstract Abstract 1807 Dasatinib (DA) is approved for use in imatinib-resistant or intolerant chronic myeloid leukemia (CML)/Philadelphia-positive acute lymphoid leukemia (Ph+ALL) and may also be useful for central nervous system (CNS) leukemia accompanied with CML/Ph+ALL; however, little is known about the relationship between DA pharmacokinetics and its ability to penetrate the blood-brain barrier. Consequently, we measured DA plasma and cerebrospinal fluid (CSF) levels by high-performance liquid chromatography in 20 samples obtained from 11 DA-treated patients (seven Ph+ALL and four lymphoid crisis CML). DA was detected in 10 CSF samples from five patients who were treated with 100 mg QD of DA (CSF C4h of detectable group; 3.526±2.604 ng/mL, 1.11–7.95 ng/mL), which was above the IC50 level for wild type BCR-ABL positive leukemia cells in vitro (0.8 nM = 0.39 ng/mL). However, DA was not detected in 10 CSF samples from 7 patients (CSF C4h of non-detectable group; <1.0 ng/mL). The concentration ratio of CSF to plasma was 3.90% (0.42-12.23%), which approached previously reported ratios for imatinib. There were significant differences in the AUC0-4 and the plasma C4h between the CSF detectable (D) and non-detectable (ND) patients (AUC0-4: 268.29±92.452 vs. 90.83±76.45, P=0.00019 by Student t-test, Figure 1; plasma C4h: 126.15±62.58 vs. 47.41±50.935, P=0.00637 by Student t-test). Moreover, there were significant correlations between CSF C4h and AUC0-4 (P<0.01, Figure 2) and between CSF C4h and plasma C2h (P<0.001), together suggesting that penetration of DA into the CSF may depend on DA plasma concentration. To investigate any influence of pharmacogenetic variation on CSF penetration, single nucleotide polymorphisms in genes involved in DA pharmacokinetics and transport (ABCB1, ABCG2, SLC22A1, SLC22A3, and CYP3A4/5) were interrogated; however, no significant correlation between CSF levels and genotype were observed. DA has a 325 fold greater potency than imatinib for inhibiting BCR-ABL tyrosine kinase, which undoubtedly influences the efficacy of DA for Philadelphia-chromosome positive CNS leukemia; however, our data suggest that clinical DA blood level monitoring may help estimate the penetration of DA to the CSF. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Identification of central nervous system genes involved in the host response to the scrapie agent during preclinical and clinical infection

2004 ◽  
Vol 85 (11) ◽  
pp. 3459-3471 ◽  
Author(s):  
Stephanie Booth ◽  
Christopher Bowman ◽  
Richard Baumgartner ◽  
Garrett Sorensen ◽  
Catherine Robertson ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Time Course ◽  
Early Stage ◽  
Expression Profiles ◽  
Clinical Stage ◽  
Disease Process ◽  
Gene Expression Profiles ◽  
Number Of Genes ◽  
Haematopoietic System

Genes that are expressed differentially in the central nervous system of mice during infection with mouse-adapted scrapie agents were identified in this study. cDNA microarrays were used to examine gene-expression profiles at early, middle (preclinical) and late (clinical) time points after inoculation. A number of genes that showed significant changes in expression during the clinical stage of disease were identified. Of these, 138 were upregulated and 20 were downregulated. A smaller number of genes showed differential expression at the early and middle stages of the disease time course. These genes are interesting, as they may reflect biological processes that are involved in the molecular pathogenesis of the prion agent. At present, little is known about the early events in the disease process that trigger neurodegeneration. Perhaps most interestingly, one group of genes that exhibited decreased expression in all tested stages of the disease was identified in this study. This cluster included four transcripts representing haematopoietic system-related genes, which suggests that the haematopoietic system is involved in the disease process from an early stage.

scholarly journals Single-cell immune repertoire and transcriptome sequencing reveals that clonally expanded and transcriptionally distinct lymphocytes populate the aged central nervous system in mice

2020 ◽  
Author(s):  
Alexander Yermanos ◽  
Daniel Neumeier ◽  
Ioana Sandu ◽  
Mariana Borsa ◽  
Ann Cathrin Waindok ◽  
...  
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
B Cells ◽  
Single Cell ◽  
Somatic Hypermutation ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cell Receptor ◽  
The Central Nervous System

AbstractNeuroinflammation plays a crucial role during ageing and various neurological conditions, including Alzheimer’s disease, multiple sclerosis and infection. Technical limitations, however, have prevented an integrative analysis of how lymphocyte immune receptor repertoires and their accompanying transcriptional states change with age in the central nervous system (CNS). Here, we leveraged single-cell sequencing to simultaneously profile B cell receptor (BCR) and T cell receptor (TCR) repertoires and accompanying gene expression profiles in young and old mouse brains. We observed the presence of clonally expanded B and T cells in the central nervous system (CNS) of aged mice. Furthermore, many of these B cells were of the IgM and IgD isotype and had low levels of somatic hypermutation. Integrating gene expression information additionally revealed distinct transcriptional profiles of these clonally expanded lymphocytes. Our findings implicate that clonally related T and B cells in the CNS of elderly mice may contribute to neuroinflammation accompanying homeostatic ageing.

Gene expression profiles in the rat central nervous system induced by JP-8 jet fuel vapor exposure

2004 ◽  
Vol 363 (3) ◽  
pp. 233-238 ◽  
Author(s):  
Baochuan Lin ◽  
Glenn D. Ritchie ◽  
John Rossi ◽  
Joseph J. Pancrazio
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Jet Fuel ◽  
Fuel Vapor

scholarly journals Detection of SARS-CoV-2 nucleic acid in CSF by ultrahigh depth sequencing in a patient with COVID-19 and neurological dysfunction: a case report

2020 ◽  
Author(s):  
Pan Xiang ◽  
Xinmin Xu ◽  
Xin Lu ◽  
Lili Gao ◽  
Huizhu Wang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Nucleic Acid ◽  
Neural Progenitor Cells ◽  
Central Nervous System Infection ◽  
Neurological Dysfunction ◽  
Human Neural Progenitor Cells ◽  
The Central Nervous System

Abstract Background: SARS-Coronavirus-2 (SARS-CoV-2), the pathogen of coronavirus disease 2019 (COVID-19), not only infects the respiratory tract, but also other organs. About a third of the inpatients of COVID-19 have neurological symptoms and in vitro experiments revealed that SARS-CoV-2 could infect human neural progenitor cells and brain organoids. However, the traditional test often reports negative owing to the low number of virus in the cerebrospinal fluid. To date, timely diagnosis of central nervous system infection of SARS-CoV-2 remains a challenge.Case presentation: On day 14 of COVID-19, seizures, maxillofacial convulsions, intractable hiccups and significant increase in intracranial pressure developed in a 56-year-old man. The RT-PCR of SARS-CoV-2 was negative. SARS-CoV-2 nucleic acid were detected in cerebrospinal fluid (CSF) by ultrahigh depth sequencing. The patient was successfully treated after 14 days of mechanical ventilation and treatment of pneumonia and neurological dysfunction.Conclusions: This case suggests SARS-CoV-2 can invade the central nervous system and relevant examinations with CSF including ultrahigh depth sequencing of SARS-CoV-2 are needed among COVID-19 patients with neurological dysfunction.

Chemotaxis of T-cells after infection of human choroid plexus papilloma cells with Echovirus 30 in an in vitro model of the blood–cerebrospinal fluid barrier

2012 ◽  
Vol 170 (1-2) ◽  
pp. 66-74 ◽  
Author(s):  
Henriette Schneider ◽  
Claudia Ellen Weber ◽  
Julia Schoeller ◽  
Ulrike Steinmann ◽  
Julia Borkowski ◽  
...  
Keyword(s):  
T Cells ◽  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
In Vitro Model ◽  
Choroid Plexus Papilloma ◽  
Echovirus 30 ◽  
Human Choroid Plexus ◽  
Vitro Model ◽  
Plexus Papilloma

scholarly journals Tumor and Cerebrospinal Fluid microRNAs in Primary Central Nervous System Lymphomas

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1647
Author(s):  
Michalina Zajdel ◽  
Grzegorz Rymkiewicz ◽  
Maria Sromek ◽  
Maria Cieslikowska ◽  
Pawel Swoboda ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Expression Profiles ◽  
Central Nervous System Lymphoma ◽  
Brain Biopsy ◽  
B Cell Lymphoma ◽  
Brain Lesions ◽  
Non Hodgkin Lymphoma ◽  
Precise Diagnosis

Primary central nervous system lymphoma (PCNSL) is a rare, highly aggressive, extranodal form of non-Hodgkin lymphoma, predominantly diagnosed as primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL). Fast and precise diagnosis of PCNSL is critical yet challenging. microRNAs, important regulators in physiology and pathology are potential biomarkers. In 131 patients with CNS DLBCL and with non-malignant brain lesions (n-ML), miR-21, miR-19b and miR-92a, miR-155, miR-196b, miR-let-7b, miR-125b, and miR-9 were examined by RT-qPCR in brain biopsy samples (formalin-fixed paraffin-embedded tissues, FFPET; CNS DLBCL, n = 52; n-ML, n = 42) and cerebrospinal fluid samples (CSF; CNS DLBCL, n = 30; n-ML, n = 23) taken for routine diagnosis. FFPET samples were split into study and validation sets. Significantly higher CSF levels of miR-21, miR-19b, and miR-92a were identified in PCNSL but not in n-ML, and differentiated PCNSL from n-ML with 63.33% sensitivity and 80.77% specificity. In FFPETs, miR-155 and miR-196b were significantly overexpressed and miR-let-7b, miR-125b, and miR-9 were downregulated in PCNSL as compared to n-ML. Combined miR-155 and miR-let-7b expression levels in FFPETs discriminated PCNSL and n-ML with a 97% accuracy. In conclusion, tissue miR-155, miR-196b, miR-9, miR-125b, and miR-let-7b expression profiles differentiate PCNSL from n-ML. PCNSL CSFs and the relevant biopsy samples are characterized by specific, different microRNA profiles. A logistic regression model is proposed to discriminate between PCNSL and non-malignant brain lesions. None of the examined microRNAs influenced overall survival of PCNSL patients. Further ongoing developments involve next generation sequencing-based profiling of biopsy and CSF samples.

scholarly journals Pharmacokinetic-Pharmacodynamic Contributions to the Convulsant Activity of Fluoroquinolones in Rats

1999 ◽  
Vol 43 (6) ◽  
pp. 1511-1515 ◽  
Author(s):  
Annie Delon ◽  
Serge Bouquet ◽  
Francois Huguet ◽  
Valerie Brunet ◽  
Philippe Courtois ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Experimental Approach ◽  
In Vitro Experiments ◽  
Methyl Group ◽  
The Central Nervous System

ABSTRACT The in vivo convulsant activities in rats of five representative fluoroquinolones (FQs), norfloxacin, enoxacin, sparfloxacin, fleroxacin, and pefloxacin, were compared. The experimental approach allowed distinction between the drugs’ ability to reach the pharmacological receptors at the level of the central nervous system (pharmacokinetic contribution) and their ability to interact with these receptors (pharmacodynamic contribution). The presence of a methyl group on the piperazine moiety decreased the pharmacodynamic contribution to the convulsant activity by severalfold, and the ratios of concentrations of the FQs in cerebrospinal fluid (CSF) to concentrations of unbound FQs in plasma varied from about 5 to 75% as a function of lipophilicity. Interestingly, FQs with the highest intrinsic convulsant activities had the lowest levels of diffusion in CSF and vice versa. This in vivo approach provides information complementary to that of in vitro experiments and should be recommended for early preclinical assessment of a new FQ’s epileptogenic risk.

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