scholarly journals Cerebrospinal Fluid Cytokines in Patients with Neurosyphilis: The Significance of Interleukin-10 for the Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Wurong Li ◽  
Wenqing Wu ◽  
Haoxiao Chang ◽  
Meijuan Jiang ◽  
Junhua Gao ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Microglial Activation ◽  
Neuronal Injury ◽  
Interleukin 10 ◽  
Diagnostic Value ◽  
Neurofilament Light ◽  
Penicillin Therapy ◽  
Csf Levels ◽  
Wbc Count ◽  
Necrosis Factor

The aim of this study was to examine the cerebrospinal fluid (CSF) concentrations of proinflammatory and anti-inflammatory cytokines in neurosyphilis (NS), analyze the differences between asymptomatic NS (ANS) and symptomatic NS (SNS), and explore the diagnostic value of these cytokines. We enrolled 45 patients with a diagnosis of NS, including 18 patients with ANS and 27 patients with SNS, whose cerebrospinal fluid (CSF) samples were collected before penicillin therapy. Twelve patients with syphilis but non-NS (NNS) were also included. We measured the CSF levels of interleukin- (IL-) 1β, IL-4, IL-6, IL-10, IL-17A, IL-21, and tumor necrosis factor- (TNF-) α; the CSF levels of the microglial activation marker soluble triggering receptor expressed on myeloid cells 2 (sTREM2); and the CSF levels of the neuronal injury marker neurofilament light proteins (NFL) using the human cytokine multiplex assay or ELISA. Of the measured cytokines in the CSF, only IL-10 levels were significantly increased in NS patients compared to NNS patients (p<0.001). In a subgroup analysis, the CSF levels of IL-10 were significantly elevated in SNS patients compared to ANS and NNS patients (p=0.024 and p<0.001, respectively). The CSF IL-10 levels had a significant correlation with the markers of microglial activation and neuronal injury, and they also correlated with CSF rapid plasma reagin (RPR) titer, CSF white blood cell (WBC) count, and CSF protein concentration. The areas under the ROC curve (AUC) of CSF IL-10 in the diagnosis of NS and ANS were 0.920 and 0.891, respectively. The corresponding sensitivities/specificities were 86.7%/91.7% and 83.3%/91.7%, respectively. Therefore, the excessive production of IL-10 might facilitate bacterial persistent infection, play an important role in the pathogenesis of NS, and associate with the progression of the disease. CSF IL-10 concentration had a useful value in the diagnosis of NS, especially in ANS.

scholarly journals Evaluation of neurofilament light chain in the cerebrospinal fluid and blood as a biomarker for neuronal damage in experimental pneumococcal meningitis

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Ngoc Dung Le ◽  
Lukas Muri ◽  
Denis Grandgirard ◽  
Jens Kuhle ◽  
David Leppert ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Single Molecule ◽  
Light Chain ◽  
Pneumococcal Meningitis ◽  
Neuronal Damage ◽  
Neuronal Injury ◽  
Health Concern ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Inflammatory Phase

Abstract Background Pneumococcal meningitis (PM) remains a global public health concern and affects all age groups. If acquired during infancy or childhood, permanent neurofunctional deficits including cognitive impairment, cerebral palsy, and secondary epilepsy are typical sequelae of neuronal injury. Determination of patients at risk for the development of brain injury and subsequent neurofunctional sequelae could help to identify patients for focused management. Neurofilament light chain (NfL) is an axonal cytoskeletal protein released upon neuronal injury into the cerebrospinal fluid (CSF) and blood. As little is known about the course of neurofilament release in the course of PM, we measured CSF and serum NfL levels longitudinally in experimental PM (ePM). Methods Eleven-day-old infant Wistar rats were infected intracisternally with Streptococcus pneumoniae and treated with ceftriaxone. At 18 and 42 h post-infection (hpi), the blood and CSF were sampled for NfL measurements by a single molecule array technology. Inflammatory cytokines and MMP-9 in CSF were quantified by magnetic bead multiplex assay (Luminex®) and by gel zymography, respectively. Results In ePM, CSF and serum NfL levels started to increase at 18 hpi and were 26- and 3.5-fold increased, respectively, compared to mock-infected animals at 42 hpi (p < 0.0001). CSF and serum NfL correlated at 18 hpi (p < 0.05, r = 0.4716) and 42 hpi (p < 0.0001, r = 0.8179). Both CSF and serum NfL at 42 hpi strongly correlated with CSF levels of IL-1β, TNF-α, and IL-6 and of MMP-9 depending on their individual kinetics. Conclusion Current results demonstrate that during the peak inflammatory phase of ePM, NfL levels in CSF and serum are the highest among CNS disease models studied so far. Given the strong correlation of CSF versus serum NfL, and its CNS-specific signal character, longitudinal measurements to monitor the course of PM could be performed based on blood sample tests, i.e., without the need of repetitive spinal taps. We conclude that NfL in the serum should be evaluated as a biomarker in PM.

scholarly journals A Case of HaNDL with Low Cerebrospinal Fluid Level of Neurofilament Light Chain

2020 ◽  
Vol 12 (3) ◽  
pp. 334-338
Author(s):  
Aysel Büsra Sisman ◽  
Muhammet Duran Bayar ◽  
Sema İçöz ◽  
Vuslat Yilmaz ◽  
Murat Kürtüncü ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Light Chain ◽  
Primary Headache ◽  
Neurological Deficits ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Cerebrospinal Fluid Level ◽  
Csf Levels ◽  
Characteristic Features ◽  
Headache Patients

Diagnosis of the syndrome of headache and neurological deficits with cerebrospinal fluid (CSF) lymphocytosis (HaNDL) is based on clinical features, and no diagnostic biomarkers are available. We present a case presenting with characteristic features of HaNDL and an MRI lesion in the splenium of corpus callosum. CSF neurofilament light chain (NFL) levels were assessed in this patient together with 7 additional HaNDL patients, 18 multiple sclerosis (MS) patients, and 15 primary headache patients. Both HaNDL and primary headache patients showed significantly lower NFL levels than MS patients. Our results suggest that increased CSF levels of NFL and neuroaxonal loss are not characteristic features of HaNDL. Neurological disorders mimicking HaNDL often present with increased levels of NFL, and thus CSF measurement of NFL might be useful in differential diagnosis of HaNDL.

scholarly journals Interleukin-10 and Soluble Tumor Necrosis Factor Receptors in Cerebrospinal Fluid of Children with Bacterial Meningitis

1996 ◽  
Vol 173 (6) ◽  
pp. 1498-1502 ◽  
Author(s):  
R. F. Kornelisse ◽  
H. F. J. Savelkoul ◽  
P. H. G. Mulder ◽  
M. H. Suur ◽  
P. J. C. van der Straaten ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Tumor Necrosis Factor ◽  
Bacterial Meningitis ◽  
Tumor Necrosis ◽  
Interleukin 10 ◽  
Tumor Necrosis Factor Receptors ◽  
Necrosis Factor

scholarly journals Glial and neuronal markers in cerebrospinal fluid predict progression in multiple sclerosis

2015 ◽  
Vol 21 (5) ◽  
pp. 550-561 ◽  
Author(s):  
M Alba Mañé Martínez ◽  
Bob Olsson ◽  
Laura Bau ◽  
Elisabet Matas ◽  
Álvaro Cobo Calvo ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Disability Progression ◽  
Neurofilament Light ◽  
Monocyte Chemoattractant Protein 1 ◽  
Neuronal Markers ◽  
Independent Prognostic Marker ◽  
Csf Levels ◽  
In Cis ◽  
T Tau

Objective: To investigate glial and neuronal biomarkers in cerebrospinal fluid (CSF) samples from patients with relapsing–remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS), and to evaluate their ability to predict conversion from CIS to clinically definite MS (CDMS) and also disability progression in MS. Methods: CSF levels of neurofilament light protein (NFL), t-tau, p-tau, glial fibrillary acidic protein (GFAP), S-100B, human chitinase 3-like 1 protein (YKL-40), monocyte chemoattractant protein-1 (MCP-1), α-sAPP and β-sAPP; and Aβ38, Aβ40 and Aβ42, were analyzed in 109 CIS patients and 192 RRMS patients. The mean follow-up time of these 301 patients was 11.7 ± 6.4 years. Results: High levels of NFL were associated with early conversion from CIS to CDMS (hazard ratio (HR) with 95% confidence interval (CI): 2.69 (1.75 – 4.15); p < 0.0001). High levels of YKL-40 and GFAP were associated with earlier progression in the Expanded Disability Status Scale (EDSS), score 3: YKL-40 (HR (95% CI): 2.78 (1.48 – 5.23); p = 0.001) and GFAP (HR (95% CI): 1.83 (1.01 – 3.35); p = 0.04). High levels of YKL-40 were associated with earlier progression to EDSS 6 (HR (95% CI): 4.57 (1.01 – 20.83); p = 0.05). Conclusions: CSF levels of NFL in CIS patients are an independent prognostic marker for conversion to CDMS. Whereas, CSF levels of YKL-40 and GFAP are independent prognostic markers for disability progression in MS.

scholarly journals High Level of Serum and Cerebrospinal Fluid of Heparan Sulfate and Hyaluronic Acid Might Be a Biomarker of Severity of Neuromyelitis Optica

2021 ◽  
Vol 12 ◽  
Author(s):  
Qi Zhang ◽  
Shanshan Pei ◽  
Zheyi Zhou ◽  
Zhanhang Wang ◽  
Yu Peng ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Hyaluronic Acid ◽  
Heparan Sulfate ◽  
Neuromyelitis Optica ◽  
Neurological Diseases ◽  
Clinical Situation ◽  
Diagnostic Value ◽  
Demyelinating Diseases ◽  
Csf Levels ◽  
High Level

BackgroundNeuromyelitis optica (NMO), multiple sclerosis (MS) and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy are idiopathic inflammatory demyelinating diseases (IIDDs) that mainly present as encephalomyelitis. Heparan sulfate (HS) and hyaluronic acid (HA) are two components of glycocalyx, a carbohydrate-rich layer on the surface of blood vessels that mediates interaction with blood. Degradation of glycocalyx in NMO is poorly understood.PurposeTo detect the serum and cerebrospinal fluid (CSF) levels of shed HS and HA and to correlate these levels with disease severity to determine their diagnostic value.MethodsWe obtained serum and CSF samples from 24 NMO patients, 15 MS patients, 10 autoimmune GFAP astrocytopathy patients, and 18 controls without non-inflammatory neurological diseases. Soluble HS and HA, and IFNγ, IL17A, and matrix metalloproteinase (MMP) 1 were detected via ELISA.ResultsSerum and CSF levels of HS, HA and related cytokines but not of plasma MMP1 were significantly elevated in these diseases. Notably, HS and HA levels were positively correlated with Expanded Disability Status Scale scores.ConclusionsOur results indicate glycocalyx degradation and inflammation in NMO, MS and autoimmune GFAP astrocytopathy. Moreover, increased shedding of HS or HA may indicate a worse clinical situation. Furthermore, therapeutic strategies that protect glycocalyx may be effective in these diseases.

scholarly journals Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology

2019 ◽  
Vol 76 (9) ◽  
pp. 1035 ◽  
Author(s):  
Claire Bridel ◽  
Wessel N. van Wieringen ◽  
Henrik Zetterberg ◽  
Betty M. Tijms ◽  
Charlotte E. Teunissen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Diagnostic Value ◽  
Neurofilament Light

scholarly journals CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection

2018 ◽  
Vol 6 (1) ◽  
pp. e512 ◽  
Author(s):  
Magnus Gisslén ◽  
Amanda Heslegrave ◽  
Elena Veleva ◽  
Aylin Yilmaz ◽  
Lars-Magnus Andersson ◽  
...  
Keyword(s):  
T Cell ◽  
Microglial Activation ◽  
Neuronal Injury ◽  
Cell Loss ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Cell Counts ◽  
Negative Controls ◽  
Hiv 1 ◽  
Hiv Negative

ObjectiveTo explore changes in CSF sTREM2 concentrations in the evolving course of HIV-1 infection.MethodsIn this retrospective cross-sectional study, we measured concentrations of the macrophage/microglial activation marker sTREM2 in CSF samples from 121 HIV-1–infected adults and 11 HIV-negative controls and examined their correlations with other CSF and blood biomarkers of infection, inflammation, and neuronal injury.ResultsCSF sTREM2 increased with systemic and CNS HIV-1 disease severity, with the highest levels found in patients with HIV-associated dementia (HAD). In untreated HIV-1–infected patients without an HAD diagnosis, levels of CSF sTREM2 increased with decreasing CD4+ T-cell counts. CSF concentrations of both sTREM2 and the neuronal injury marker neurofilament light protein (NFL) were significantly associated with age. CSF sTREM2 levels were also independently correlated with CSF NFL. Notably, this association was also observed in HIV-negative controls with normal CSF NFL. HIV-infected patients on suppressive antiretroviral treatment had CSF sTREM2 levels comparable to healthy controls.ConclusionsElevations in CSF sTREM2 levels, an indicator of macrophage/microglial activation, are a common feature of untreated HIV-1 infection that increases with CD4+ T-cell loss and reaches highest levels in HAD. The strong and independent association between CSF sTREM2 and CSF NFL suggests a linkage between microglial activation and neuronal injury in HIV-1 infection. CSF sTREM2 has the potential of being a useful biomarker of innate CNS immune activation in different stages of untreated and treated HIV-1 infection.

High Levels of Interleukin 10 and Tumor Necrosis Factor   in Cerebrospinal Fluid During the Onset of Bacterial Meningitis

1995 ◽  
Vol 21 (1) ◽  
pp. 220-222 ◽  
Author(s):  
A. M. van Furth ◽  
E. M. Seijmonsbergen ◽  
J. A. M. Langermans ◽  
P. H. P. Groeneveld ◽  
C. E. de Bel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Tumor Necrosis Factor ◽  
Bacterial Meningitis ◽  
Tumor Necrosis ◽  
Interleukin 10 ◽  
Necrosis Factor

Effects of tacrolimus on hemispheric water content and cerebrospinal fluid levels of glutamate, hypoxanthine, interleukin-6, and tumor necrosis factor-α following controlled cortical impact injury in rats

2001 ◽  
Vol 94 (5) ◽  
pp. 782-787 ◽  
Author(s):  
John F. Stover ◽  
Britta Schöning ◽  
Oliver W. Sakowitz ◽  
Christian Woiciechowsky ◽  
Andreas W. Unterberg
Keyword(s):  
Cerebrospinal Fluid ◽  
Tissue Damage ◽  
Tumor Necrosis ◽  
Edema Formation ◽  
Content Type ◽  
Controlled Cortical Impact Injury ◽  
Csf Levels ◽  
Impact Injury ◽  
Necrosis Factor ◽  
Fine Print

Object. Disturbance of calcium homeostasis contributes to evolving tissue damage and energetic impairment following traumatic brain injury (TBI). Calcium-mediated activation of calcineurin results in production of tissue-damaging nitric oxide and free oxygen radicals. Inhibition of calcineurin induced by the immunosuppressant tacrolimus (FK506) has been shown to reduce structural and functional damage after ischemia. The aims of the present study were to investigate time- and dose-dependent short-term antiedematous effects of tacrolimus following TBI. Methods. A left temporoparietal contusion (controlled cortical impact injury [CCII]) was induced in 51 male Sprague—Dawley rats. Tacrolimus (1 or 3 mg/kg body weight) was administered by a single intraperitoneal injection at 5 minutes, 30 minutes, or 4 hours after CCII occurred. Control rats received physiological saline. Water contents of traumatized and nontraumatized hemispheres, as well as cerebrospinal fluid (CSF) levels of mediators reflecting tissue damage (the proinflammatory cytokines interleukin [IL]-6 and tumor necrosis factor [TNF]—α, the excitotoxin glutamate, and the adenosine triphosphate—degradation product hypoxanthine), were determined 24 hours after trauma. Although CSF levels of IL-6 and TNFα were completely suppressed by tacrolimus at all time points and at both concentrations, CSF levels of glutamate and hypoxanthine, as well as edema formation, were only marginally influenced. Significant reduction of cerebral water content was confined to nontraumatized hemispheres. In addition, the higher dose of tacrolimus failed to exert significant antiedematous effects on traumatized hemispheres. Conclusions. Under the present study design, the potency of tacrolimus in reducing edema formation following CCII seems limited. However, its immunosuppressive effects could be of value in influencing the posttraumatic inflammatory response known to aggravate tissue damage.

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