scholarly journals Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 43 ◽  
Author(s):  
Daniel Appelgren ◽  
Helena Enocsson ◽  
Barbro H. Skogman ◽  
Marika Nordberg ◽  
Linda Perander ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Hydrolytic Enzymes ◽  
Neutrophil Extracellular Trap ◽  
Cns Infections ◽  
Neurotropic Viruses ◽  
Csf Levels ◽  
Innate Defence

Neutrophils operate as part of the innate defence in the skin and may eliminate the Borrelia spirochaete via phagocytosis, oxidative bursts, and hydrolytic enzymes. However, their importance in Lyme neuroborreliosis (LNB) is unclear. Neutrophil extracellular trap (NET) formation, which is associated with the production of reactive oxygen species, involves the extrusion of the neutrophil DNA to form traps that incapacitate bacteria and immobilise viruses. Meanwhile, NET formation has recently been studied in pneumococcal meningitis, the role of NETs in other central nervous system (CNS) infections has previously not been studied. Here, cerebrospinal fluid (CSF) samples from clinically well-characterised children (N = 111) and adults (N = 64) with LNB and other CNS infections were analysed for NETs (DNA/myeloperoxidase complexes) and elastase activity. NETs were detected more frequently in the children than the adults (p = 0.01). NET presence was associated with higher CSF levels of CXCL1 (p < 0.001), CXCL6 (p = 0.007), CXCL8 (p = 0.003), CXCL10 (p < 0.001), MMP-9 (p = 0.002), TNF (p = 0.02), IL-6 (p < 0.001), and IL-17A (p = 0.03). NETs were associated with fever (p = 0.002) and correlated with polynuclear pleocytosis (rs = 0.53, p < 0.0001). We show that neutrophil activation and active NET formation occur in the CSF samples of children and adults with CNS infections, mainly caused by Borrelia and neurotropic viruses. The role of NETs in the early phase of viral/bacterial CNS infections warrants further investigation.

Penetration of VP 16-213 into cerebrospinal fluid after high-dose intravenous administration.

1984 ◽  
Vol 2 (3) ◽  
pp. 215-220 ◽  
Author(s):  
P E Postmus ◽  
J J Holthuis ◽  
H Haaxma-Reiche ◽  
N H Mulder ◽  
L M Vencken ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
Cns Metastases ◽  
Csf Levels ◽  
Dose Levels

VP 16-213 in standard doses is active against a number of solid tumors. Its penetration into the cerebrospinal fluid (CSF) is very limited at these dose levels. In 10 patients treated with high-dose VP 16-213 (0.9-2.5 g/m2), CSF levels of up to 0.54 microgram/mL were detected. In two patients with central nervous system (CNS) metastases of small cell lung cancer (SCLC) a response was seen after 1.0 and 1.5 g/m2 intravenously. High-dose VP 16-213 can possibly play a role in the treatment of CNS metastases of SCLC. Its application in late intensification regimens as a form of prophylaxis of CNS metastases should be investigated.

scholarly journals Cerebrospinal fluid anandamide levels, cannabis use and psychotic-like symptoms

2013 ◽  
Vol 202 (5) ◽  
pp. 381-382 ◽  
Author(s):  
Celia J. A. Morgan ◽  
Emma Page ◽  
Carola Schaefer ◽  
Katharine Chatten ◽  
Amod Manocha ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Lower Risk ◽  
Endocannabinoid System ◽  
Cannabis Use ◽  
Psychotic Symptoms ◽  
Csf Levels ◽  
Drug Free

SummaryAnandamide is a ligand of the endocannabinoid system. Animals show a depletion following repeated Δ9-tetrahydrocannabinol (THC) administration but the effect of cannabis use on central nervous system levels of endocannabinoids has not been previously examined in humans. Cerebrospinal fluid (CSF) levels of the endocannabinoids anandamide, 2-arachidonoylglycerol (2-AG) and related lipids were tested in 33 volunteers (20 cannabis users). Lower levels of CSF anandamide and higher levels of 2-AG in serum were observed in frequent compared with infrequent cannabis users. Levels of CSF anandamide were negatively correlated with persisting psychotic symptoms when drug-free. Higher levels of anandamide are associated with a lower risk of psychotic symptoms following cannabis use.

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 When Ventricular Cerebrospinal Fluid Assessment Misleads: Basal Meningitis and the Importance of Lumbar Puncture Sampling

2019 ◽  
Vol 6 (7) ◽  
Author(s):  
Sadid F Khan ◽  
Thornton Macauley ◽  
Steven Y C Tong ◽  
Ouli Xie ◽  
Carly Hughes ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Lumbar Puncture ◽  
Cns Infection ◽  
Pathophysiological Mechanisms ◽  
Cns Infections ◽  
Fluid Assessment ◽  
Composition Gradients

Abstract The diagnosis of central nervous system (CNS) infection relies upon analysis of cerebrospinal fluid (CSF). We present 4 cases of CNS infections associated with basal meningitis and hydrocephalus with normal ventricular CSF but grossly abnormal lumbar CSF. We discuss CSF ventricular–lumbar composition gradients and putative pathophysiological mechanisms and highlight clinical clues for clinicians.

The role of metabolites and the role of histo-hematological barriers in the regulation of body functions. (End)

1937 ◽  
Vol 33 (5) ◽  
pp. 523-532
Author(s):  
L. S. Stern
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
General Circulation ◽  
Physiological State ◽  
The State ◽  
The Central Nervous System ◽  
The Brain ◽  
Physiological Systems

Evaluation of the results obtained in the study of the effect of cerebrospinal fluid on various physiological systems is complicated by the fact that the composition of the cerebrospinal fluid depends to a large extent on the state of the blood-brain barrier, and thus reflects not only a certain physiological state of the central nervous system. There is no doubt that the metabolic products of the brain, secreted into the cerebrospinal fluid, exert their effect not only on the activity of various parts of the brain and on the coordination of their functions, but due to the rapid transition of these substances from the cerebrospinal fluid into the general circulation, they also affect as a humoral a factor on the function of other physiological systems, as it was revealed in a number of experiments carried out in recent years in our laboratories. For example, it turned out that under various influences (direct irritation of the central nervous system in experimental epilepsy, irritation of the sensory nerves associated with severe pain, traumatic shock, toxemic or chemical shock, as well as starvation, prolonged insomnia, etc.) - substances appear in the cerebrospinal fluid that affect the state and activity of the cardiovascular system, the tone of smooth muscles, the excitability of the central nervous system, etc. These are the results of the work of our employees: Zeitlin, Weiss, Harles, Voskresensky, Gromakovskaya , Bazarova, Gotsman, Komarova and others. Work in this direction continues at the present time.

scholarly journals Chemokines and Chemokine Receptors in Multiple Sclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Wenjing Cheng ◽  
Guangjie Chen
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Autoimmune Disease ◽  
Chemokine Receptors ◽  
Cell Subset ◽  
Small Peptide

Multiple sclerosis is an autoimmune disease with classical traits of demyelination, axonal damage, and neurodegeneration. The migration of autoimmune T cells and macrophages from blood to central nervous system as well as the destruction of blood brain barrier are thought to be the major processes in the development of this disease. Chemokines, which are small peptide mediators, can attract pathogenic cells to the sites of inflammation. Each helper T cell subset expresses different chemokine receptors so as to exert their different functions in the pathogenesis of MS. Recently published results have shown that the levels of some chemokines and chemokine receptors are increased in blood and cerebrospinal fluid of MS patients. This review describes the advanced researches on the role of chemokines and chemokine receptors in the development of MS and discusses the potential therapy of this disease targeting the chemokine network.

scholarly journals Identification of a New Cyclovirus in Cerebrospinal Fluid of Patients with Acute Central Nervous System Infections

mBio ◽  
2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Le Van Tan ◽  
H. Rogier van Doorn ◽  
Ho Dang Trung Nghia ◽  
Tran Thi Hong Chau ◽  
Le Thi Phuong Tu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Unknown Etiology ◽  
Healthy Children ◽  
Detection Rates ◽  
Cns Infections ◽  
Food Borne ◽  
Animal Reservoirs ◽  
Substantial Morbidity

ABSTRACTAcute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus.IMPORTANCEAcute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology frequently remains unknown, which hampers development of therapeutic or preventive strategies. Hence, identification of novel pathogens is essential and is facilitated by current next-generation sequencing-based methods. Using such technology, we identified and characterized the full genome of a novel cyclovirus in cerebrospinal fluid (CSF) specimens from two Vietnamese patients with CNS infections of unknown etiology, which was subsequently detected in none of 122 CSF specimens from patients with noninfectious neurological disorders but 4% of 642 CSF specimens from Vietnamese patients with suspected or confirmed CNS infections. Similar detection rates in feces from healthy children suggested food-borne or orofecal transmission routes, while frequent detection in feces from Vietnamese pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further studies are needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus.

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