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1.
J Stroke Cerebrovasc Dis ; 29(9): 105054, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32807460

RESUMEN

BACKGROUND: Phospholipids and sphingolipids are cell membrane components, that participate in signaling events and regulate a wide variety of vital cellular processes. Sphingolipids are involved in ischemic stroke pathophysiology. Throughout cleavage of membrane sphingomyelin by sphingomyelinase in stroke patients, it results in increased Ceramide (Cer) levels in brain tissue. Different studies showed the evidence that sphingomyelinase with Cer production induces expression of interleukin (IL)-6 and have vasoconstrictive proprieties. With this study, we intend to evaluate cerebrospinal fluid (CSF) lipid profile changes in a rabbit closed cranium subarachnoid hemorrhage (SAH) model. METHODS: A total of 14 New Zealand white rabbits were randomly allocated either to SAH or sham group. In the first group SAH was induced by extracranial-intracranial shunting from the subclavian artery into the cisterna magna. Intracranial pressure (ICP) and arterial blood pressure were continuously monitored. Digital subtraction angiography of the basilar artery, CSF and blood samples were performed at day 0 pre SAH and on day 3 post SAH. The amount of IL-6 and various lipids in CSF were quantified using ELISA and Liquid Chromatography-Mass Spectrometry respectively. Cell death was detected in bilateral basal cortex, hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: SAH Induction led to acute increase of ICP and increased delayed cerebral vasospasm (DCVS). At follow up CSF IL-6 levels showed a significant increase compared to baseline. Between baseline and follow up there were no significant differences in any of the measured CSF Lipids irrespective of subgroups. No relevant correlation was found between IL-6 and any of the sphingolipids. We found a correlation between baseline and follow up for the phospholipids phosphatidylethanolamine and phosphatidylcholine. CONCLUSIONS: Neuronal apoptosis, DCVS and IL-6 seems not to be related to changes in CSF lipid profiles except for PEA and PC in a rabbit closed cranium SAH model.


Asunto(s)
Arteria Basilar/fisiopatología , Interleucina-6/líquido cefalorraquídeo , Lípidos/líquido cefalorraquídeo , Neuronas/metabolismo , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Vasoconstricción , Vasoespasmo Intracraneal/líquido cefalorraquídeo , Animales , Apoptosis , Arteria Basilar/diagnóstico por imagen , Biomarcadores/líquido cefalorraquídeo , Modelos Animales de Enfermedad , Interleucina-6/biosíntesis , Presión Intracraneal , Neuronas/patología , Fosfatidilcolinas/líquido cefalorraquídeo , Fosfatidiletanolaminas/líquido cefalorraquídeo , Proyectos Piloto , Conejos , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/patología , Hemorragia Subaracnoidea/fisiopatología , Vasoespasmo Intracraneal/diagnóstico por imagen , Vasoespasmo Intracraneal/patología , Vasoespasmo Intracraneal/fisiopatología
3.
Neurology ; 95(10): 445-449, 2020 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-32586897

RESUMEN

Here, we report a case of COVID-19-related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.


Asunto(s)
Encéfalo/diagnóstico por imagen , Infecciones por Coronavirus/líquido cefalorraquídeo , Leucoencefalitis Hemorrágica Aguda/líquido cefalorraquídeo , Neumonía Viral/líquido cefalorraquídeo , ARN Viral/líquido cefalorraquídeo , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Betacoronavirus/genética , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/terapia , Femenino , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Interleucina-6/líquido cefalorraquídeo , Leucoencefalitis Hemorrágica Aguda/diagnóstico por imagen , Leucoencefalitis Hemorrágica Aguda/fisiopatología , Leucoencefalitis Hemorrágica Aguda/terapia , Imagen por Resonancia Magnética , Persona de Mediana Edad , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Pandemias , Intercambio Plasmático , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/fisiopatología , Neumonía Viral/terapia , Reacción en Cadena en Tiempo Real de la Polimerasa , Tomografía Computarizada por Rayos X , Tropismo Viral , Proteínas tau/líquido cefalorraquídeo
4.
Ann Neurol ; 88(2): 423-427, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32418288

RESUMEN

Coronavirus disease 2019 (COVID-19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been described in patients with severe respiratory distress. Here, we described the case of a 60-year-old patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but only mild respiratory abnormalities who developed an akinetic mutism attributable to encephalitis. Magnetic resonance imaging was negative, whereas electroencephalography showed generalized theta slowing. Cerebrospinal fluid analyses during the acute stage were negative for SARS-CoV-2, positive for pleocytosis and hyperproteinorrachia, and showed increased interleukin-8 and tumor necrosis factor-α concentrations. Other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of cerebrospinal fluid parameters was observed after high-dose steroid treatment, thus arguing for an inflammatory-mediated brain involvement related to COVID-19. ANN NEUROL 2020;88:423-427.


Asunto(s)
Mutismo Acinético/fisiopatología , Antivirales/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Encefalitis/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Metilprednisolona/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Betacoronavirus , Infecciones por Coronavirus/líquido cefalorraquídeo , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/fisiopatología , Combinación de Medicamentos , Electroencefalografía , Encefalitis/líquido cefalorraquídeo , Encefalitis/complicaciones , Encefalitis/fisiopatología , Humanos , Hidroxicloroquina/uso terapéutico , Interleucina-6/líquido cefalorraquídeo , Interleucina-8/líquido cefalorraquídeo , Lopinavir/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/líquido cefalorraquídeo , Neumonía Viral/complicaciones , Neumonía Viral/fisiopatología , Ritonavir/uso terapéutico , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo , Microglobulina beta-2/líquido cefalorraquídeo
5.
J Clin Neurosci ; 75: 176-180, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32217048

RESUMEN

Data indexing the contribution of various immuno-inflammatory components in the cerebrospinal fluid (CSF) towards the pathophysiology of Guillain Barré Syndrome (GBS) are limited. Th17 pathway plays crucial role in many immune mediated disorders of the nervous system. This study was aimed at exploring the role of Th17 pathway related cytokines in the CSF of patients with GBS. Levels of multiple key cytokines of Th17 pathway in CSF of patients with GBS (N = 37) and controls (N = 37) were examined in this prospective study using Bio-plex Pro Human Th17 cytokine assays in a Multiplex Suspension Array platform. The findings were correlated with clinical features and electrophysiological subtypes. Three key cytokines of Th17 pathway (IL-6, IL-17A and IL-22) were significantly elevated in CSF of patients with GBS as compared to controls. There was a positive correlation between the levels of IL-6 and IL-17A as well as between the levels of IL-17A and IL-22 in the CSF of patients with GBS. The CSF levels of IL-6 and IL-22 were negatively correlated with the duration of symptoms of GBS. None of the studied cytokines correlated with functional disability scores at admission to hospital or with the electrophysiological subtypes. Identification of Th17 pathway signatures in CSF sheds more insights into the pathogenic role of Th17 cells in GBS. These findings complement the contemporary knowledge and tender further support towards the involvement of Th17 pathway in GBS.


Asunto(s)
Síndrome de Guillain-Barré/líquido cefalorraquídeo , Interleucina-17/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Interleucinas/líquido cefalorraquídeo , Transducción de Señal/fisiología , Células Th17/metabolismo , Adulto , Biomarcadores/líquido cefalorraquídeo , Citocinas/líquido cefalorraquídeo , Citocinas/inmunología , Femenino , Síndrome de Guillain-Barré/inmunología , Humanos , Interleucina-17/inmunología , Interleucina-6/inmunología , Interleucinas/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Células Th17/inmunología
6.
Pediatr Infect Dis J ; 39(3): 239-243, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32032308

RESUMEN

BACKGROUND: Borrelia burgdorferi and tick-borne encephalitis (TBE) virus are 2 types of tick-borne pathogens that can cause central nervous system infection. Routine diagnostics have so far included analysis of cerebrospinal fluid (CSF) cell numbers, CSF serology for Borrelia burgdorferi and serum serology for TBE virus. However, early diagnosis may be difficult based on antibody detection which takes time to analyze, and with the possibility of false negative results, thus delaying treatment. Cytokine analyses are becoming increasingly available in clinical routine care and may offer important information. METHODS: Fifteen cytokines and chemokines were measured in the CSF from the diagnostic lumbar puncture of 37 children with TBE, 34 children with neuroborreliosis and 19 children without evidence of central nervous system infection, using Luminex technology. RESULTS: Significantly higher levels of proinflammatory interleukin-6 were detected in the samples from TBE-infected children, when compared with neuroborreliosis or controls. In comparison, children with neuroborreliosis had significantly higher levels of interleukin-7, interleukin-8, interleukin-10, and interleukin-13 when compared with TBE infected or controls. Furthermore, the ratio between interleukin-6 and interleukin-10 was significantly different between the 2 types of tick-borne infections. CONCLUSIONS: The interleukin-6/interleukin-10 ratio can be used as a rapid diagnostic cue upon suspected tick-borne infection, enabling fast and correct treatment. Also, in serology-negative results, such information may strengthen a clinical suspicion.


Asunto(s)
Virus de la Encefalitis Transmitidos por Garrapatas , Encefalitis Transmitida por Garrapatas/líquido cefalorraquídeo , Encefalitis Transmitida por Garrapatas/diagnóstico , Interleucina-10/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Biomarcadores , Quimiocinas/líquido cefalorraquídeo , Citocinas/líquido cefalorraquídeo , Encefalitis Transmitida por Garrapatas/virología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Pronóstico
7.
Biomarkers ; 25(2): 171-178, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31916867

RESUMEN

Purpose: Given the challenge in the diagnosis of bacterial meningitis (BM), we assessed different cytokines in the cerebrospinal fluid (CSF) of antibiotics pre-treated patients.Materials and methods: Laboratory tests and polymerase chain reaction (PCR) were performed for 480 CSF samples from children (2 m to 14 y), suspicious to meningitis and pre-treated with antibiotics, to detect bacterial and viral aetiologies. Sixty-one CSF were included and the levels of 13 cytokines such as IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α were measured using flow-cytometry.Results: All bacterial cultures were negative, but 29 and eight CSF were positive for bacterial and viral agents by PCR. IL-6, IL-10 and IFN-γ were significantly up-regulated in BM. T helper (Th) subset cytokines showed significant upregulation of Th1, Th2, Th17, Th22 and Tfh cytokines in BM. Common Th subsets cytokines (IL-6, IL-10 and TNF-α) were significantly different between the study groups. ROC curve analysis revealed good AUC for common Th related cytokines in discriminating BM.Conclusions: In pre-treated BM patients with negative bacterial cultures, cytokines IL-6, IL-10 and IFN-γ can predict BM which could be beneficial for rapid diagnosis and treatment to decrease the sequela of the disease.


Asunto(s)
Profilaxis Antibiótica , Citocinas/líquido cefalorraquídeo , Meningitis Bacterianas/diagnóstico , Linfocitos T Colaboradores-Inductores/inmunología , Adolescente , Biomarcadores/líquido cefalorraquídeo , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Interferón gamma/líquido cefalorraquídeo , Interleucina-10/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Masculino , Meningitis Bacterianas/tratamiento farmacológico , Pediatría/métodos
8.
Neurobiol Aging ; 85: 96-103, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31733942

RESUMEN

The APOE-ε4 genotype is a risk factor for late-onset Alzheimer's disease (AD) as well as vascular pathology. Given the increased risk of blood-brain barrier (BBB) dysfunction and inflammation among APOE-ε4 carriers, we aimed to examine whether BBB dysfunction and inflammation contribute to the relationship between APOE and AD key pathologies, as measured in the cerebrospinal fluid (CSF). We applied bootstrapped regression and path analyses involving Q-albumin CSF/plasma ratio (a BBB/blood-CSF barrier function marker), interleukins (IL-1ß, IL-6, and IL-12p70; inflammation markers), and CSF p-Tau181 and amyloid-ß1-42 (AD pathology markers) of 97 participants (aged 38-83 years) from a university memory clinic. Our results showed that relationship between BBB dysfunction and AD pathology is modulated by IL-6 and these associations appear to be driven by the APOE-ε4 genotype. This suggests that APOE-ε4-related vascular factors are also part of the pathway to AD pathology, in synergy with an elevated immune response, and could become targets for trials focused on delaying AD.


Asunto(s)
Enfermedad de Alzheimer/patología , Apolipoproteínas E/genética , Barrera Hematoencefálica/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/genética , Ciclofosfamida/análogos & derivados , Femenino , Humanos , Inflamación , Interleucina-6/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Riesgo
9.
J Microbiol Immunol Infect ; 53(2): 216-224, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30448438

RESUMEN

BACKGROUND: There has been a great deal of evidence indicating that cytokines participate in meningeal inflammation. Different cytokine profiles may be presented in central nervous system (CNS) infection due to different pathogens. We have attempted to investigate cytokine profiles in cerebrospinal fluid (CSF) of patients with CNS infection. METHODS: Forty-three patients with CNS infection including tuberculous meningitis, purulent meningitis and cryptococcal meningitis were enrolled and 11 patients with normal CSF were enrolled as control group. The concentrations of Th1-, Th2- and Th17-type cytokines in CSF were detected using multiplex cytokine assay. Furthermore, the correlation between CSF cytokines and CSF parameters in CNS infection was analyzed. RESULTS: The CSF levels of IL-1ß, IL-4, IL-6, IL-10, IL-17, IL-23, IL-33, IFN-γ, TNF-α and sCD40L among the patients with CNS infection were all higher than control group (all P < 0.05). A remarkable elevation of CSF IL-6 in the patients with CNS infection was observed with the least overlap of the CSF concentrations compared to controls. Moreover, CSF IL-6 levels were strongly negatively correlated with CSF glucose and the CSF/blood glucose ratio (r = -0.4375, P = 0.0042; r = -0.4991, P = 0.0009). CONCLUSIONS: The excessive activation of immune response characterized by elevated levels of CSF Th1-, Th2- and Th17-type cytokines has been observed during CNS infection. Furthermore, we observed negative correlations between CSF IL-6 levels and CSF glucose and CSF/blood glucose ratio in CNS infection. And we suggested that combined CSF IL-6 levels with CSF glucose may serve as a novel biomarker pool for the differential of CNS infection.


Asunto(s)
Citocinas/líquido cefalorraquídeo , Hospitales Generales , Meningitis/líquido cefalorraquídeo , Centros de Atención Terciaria , Adulto , Anciano , Biomarcadores/líquido cefalorraquídeo , Glucemia , Líquido Cefalorraquídeo/química , China , Cryptococcus neoformans , Citocinas/metabolismo , Femenino , Glucosa , Humanos , Interleucina-6/líquido cefalorraquídeo , Masculino , Meningitis/diagnóstico , Meningitis/microbiología , Meningitis Criptocócica , Persona de Mediana Edad , Células TH1 , Células Th17 , Células Th2 , Adulto Joven
10.
Medicine (Baltimore) ; 98(52): e18464, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31876729

RESUMEN

Enterovirus 71 (EV71) is an important etiological agent of hand, foot, and mouth disease (HFMD), which can also lead to severe neurological complications (eg, encephalitis) in young children. Although a series of reports on EV71 infection have been published, the pathogenic mechanism of EV71 infection is still not fully understood.We evaluated the cerebrospinal fluid (CSF) levels of the inflammatory cytokines interleukin (IL)-8, IL-1ß, IL-6, IL-10, tumor necrosis factor (TNF)-α, and IL-12p70 in 88 children with EV71-related encephalitis and 19 children with febrile convulsion (FC) with the use of commercial cytometric bead array kits.The levels of IL-8, IL-1ß, IL-6, and IL-10 in CSF were significantly higher in encephalitis group when compared with those observed in FC group, while no significant changes were noted in the levels of TNF-α and IL-12p70. In addition, significant and positive correlations among CSF IL-8, IL-1ß, IL-6, and IL-10 were observed in encephalitis group. Furthermore, receiver operator characteristic analysis determined a cut-off value of 10.62 pg/mL for IL-6 to discriminate encephalitis patients from FCs with the sensitivity and specificity of 89.8% and 84.2%, respectively. Moreover, logistic regression analyses revealed that IL-6 was an independent predictor of EV71-related encephalitis (odds ratio = 23.241, P < .001).Our results indicate that 4 inflammatory cytokines (IL-8, IL-1ß, IL-6, and IL-10) play important roles in the pathogenesis of EV71 infection. IL-6 may be used for the evaluation of EV71-related encephalitis and as a potential therapy candidate for EV71 infection.


Asunto(s)
Citocinas/líquido cefalorraquídeo , Encefalitis Viral/líquido cefalorraquídeo , Enterovirus Humano A , Enfermedad de Boca, Mano y Pie/líquido cefalorraquídeo , Preescolar , China/epidemiología , Encefalitis Viral/virología , Femenino , Enfermedad de Boca, Mano y Pie/virología , Humanos , Lactante , Interleucina-10/líquido cefalorraquídeo , Interleucina-12/líquido cefalorraquídeo , Interleucina-1beta/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Interleucina-8/líquido cefalorraquídeo , Masculino , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo
11.
Int J Mol Sci ; 20(18)2019 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-31505901

RESUMEN

Upon peripheral nerve injury, vesicular ATP is released from damaged primary afferent neurons. This extracellular ATP subsequently activates purinergic receptors of the spinal cord, which play a critical role in neuropathic pain. As an inhibitor of the vesicular nucleotide transporter (VNUT), Evans blue (EB) inhibits the vesicular storage and release of ATP in neurons. Thus, we tested whether EB could attenuate neuropathic pain behavior induced by spinal nerve ligation (SNL) in rats by targeting VNUT. An intrathecal injection of EB efficiently attenuated mechanical allodynia for five days in a dose-dependent manner and enhanced locomotive activity in an SNL rat model. Immunohistochemical analysis showed that EB was found in VNUT immunoreactivity on neurons in the dorsal root ganglion and the spinal dorsal horn. The level of ATP in cerebrospinal fluid in rats with SNL-induced neuropathic pain decreased upon administration of EB. Interestingly, EB blocked ATP release from neurons, but not glial cells in vitro. Eventually, the loss of ATP decreased microglial activity in the ipsilateral dorsal horn of the spinal cord, followed by a reduction in reactive oxygen species and proinflammatory mediators, such as interleukin (IL)-1ß and IL-6. Finally, a similar analgesic effect of EB was demonstrated in rats with monoiodoacetate-induced osteoarthritis (OA) pain. Taken together, these data demonstrate that EB prevents ATP release in the spinal dorsal horn and reduces the ATP/purinergic receptor-induced activation of spinal microglia followed by a decline in algogenic substances, thereby relieving neuropathic pain in rats with SNL.


Asunto(s)
Adenosina Trifosfato/líquido cefalorraquídeo , Azul de Evans/farmacología , Neuralgia , Columna Vertebral , Animales , Modelos Animales de Enfermedad , Ganglios Espinales/metabolismo , Ganglios Espinales/patología , Ganglios Espinales/fisiopatología , Interleucina-1beta/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Masculino , Neuralgia/líquido cefalorraquídeo , Neuralgia/tratamiento farmacológico , Neuralgia/patología , Neuralgia/fisiopatología , Neuronas/metabolismo , Neuronas/patología , Ratas , Ratas Sprague-Dawley , Columna Vertebral/metabolismo , Columna Vertebral/patología , Columna Vertebral/fisiopatología
12.
Neurorehabil Neural Repair ; 33(10): 825-835, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31431121

RESUMEN

Background: Synaptic plasticity helps in reducing the clinical expression of brain damage and represents a useful mechanism to compensate the negative impact of new brain lesions in multiple sclerosis (MS). Inflammation, altering synaptic plasticity, could negatively influence the disease course in relapsing-remitting MS (RR-MS). Objective: In the present study, we explored whether interleukin (IL)-6, a major proinflammatory cytokine involved in MS pathogenesis, alters synaptic plasticity and affects the ability to compensate for ongoing brain damage. Methods: The effect of IL-6 incubation on long-term potentiation (LTP) induction was explored in vitro, in mice hippocampal slices. We also explored the correlation between the cerebrospinal fluid (CSF) levels of this cytokine and the LTP-like effect induced by the paired associative stimulation (PAS) in a group of RR-MS patients. Finally, we examined the correlation between the CSF levels of IL-6 at the time of diagnosis and the prospective disease activity in a cohort of 150 RR-MS patients. Results: In vitro LTP induction was abolished by IL-6. Consistently, in patients with MS, a negative correlation emerged between IL-6 CSF concentrations and the effect of PAS. In MS patients, longer disease duration before diagnosis was associated with higher IL-6 CSF concentrations. In addition, elevated CSF levels of IL-6 were associated with greater clinical expression of new inflammatory brain lesions, unlike in patients with low or absent IL-6 concentrations, who had a better disease course. Conclusions: IL-6 interfering with synaptic plasticity mechanisms may impair the ability to compensate the clinical manifestation of new brain lesions in RR-MS patients.


Asunto(s)
Progresión de la Enfermedad , Potenciales Evocados Motores , Hipocampo , Interleucina-6/metabolismo , Potenciación a Largo Plazo , Esclerosis Múltiple , Plasticidad Neuronal , Adulto , Animales , Aprendizaje por Asociación , Potenciales Evocados Motores/fisiología , Femenino , Hipocampo/metabolismo , Hipocampo/fisiopatología , Humanos , Interleucina-6/líquido cefalorraquídeo , Potenciación a Largo Plazo/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/fisiopatología , Plasticidad Neuronal/fisiología , Estimulación Magnética Transcraneal
13.
PLoS One ; 14(7): e0219987, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31356620

RESUMEN

BACKGROUND: The recognition of active inflammation in the central nervous system (CNS) in the absence of infectious agents is challenging. The present study aimed to determine the diagnostic relevance of five selected chemo/cytokines in the recognition of CNS inflammation and in the context of traditional cerebrospinal fluid (CSF) biomarkers (white blood cell [WBC] counts, oligoclonal bands, protein levels, CSF/serum albumin ratios) and clinical diagnoses. METHODS: C-C and C-X-C motif ligands (CCL2, CXCL8, 10 and 13) and interleukin (IL) 6 levels in the CSF and serum from 37 control and 87 symptomatic children with ten different (mostly noninfectious) inflammatory CNS disorders (16 of which had follow-up samples after recovery) were determined using Luminex multiple bead technology and software. Nonparametric tests were used; p < 0.05 was considered statistically significant. Receiver operating characteristic curves were constructed to analyze controls and 1) all symptomatic samples or 2) symptomatic samples without CSF pleocytosis. RESULTS: Compared with the control CSF samples, levels of all investigated chemo/cytokines were increased in symptomatic CSF samples, and only IL-6 remained elevated in recovery samples (p ≤ 0.001). CSF CXCL-13 levels (> 10.9 pg/mL) were the best individual discriminatory criterion to differentiate neuroinflammation (specificity/sensitivity: 97/72% and 97/61% for samples without pleocytosis), followed by CSF WBC counts (specificity/sensitivity: 97/62%). The clinical utility of the remaining CSF chemo/cytokine levels was determined in descending order of sensitivities corresponding to thresholds that ensured 97% specificity for neuroinflammation in samples without pleocytosis (pg/mL; sensitivity %): IL-6 (3.8; 34), CXCL8 (32; 26), CXCL10 (317; 24) and CCL2 (387; 10). Different diagnosis-related patterns of CSF chemo/cytokines were observed. CONCLUSIONS: The increased CSF level of CXCL13 was the marker with the greatest predictive utility for the general recognition of neuroinflammation among all of the individually investigated biomarkers. The potential clinical utility of chemo/cytokines in the differential diagnosis of neuroinflammatory diseases was identified.


Asunto(s)
Biomarcadores/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso Central/diagnóstico , Quimiocinas/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Adolescente , Biomarcadores/sangre , Recuento de Células Sanguíneas , Enfermedades del Sistema Nervioso Central/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso Central/inmunología , Quimiocina CCL2/sangre , Quimiocina CCL2/líquido cefalorraquídeo , Quimiocina CXCL10/sangre , Quimiocina CXCL10/líquido cefalorraquídeo , Quimiocina CXCL13/sangre , Quimiocina CXCL13/líquido cefalorraquídeo , Quimiocinas/sangre , Niño , Preescolar , Femenino , Humanos , Interleucina-6/sangre , Interleucina-8/sangre , Interleucina-8/líquido cefalorraquídeo , Masculino , Curva ROC
14.
Metab Brain Dis ; 34(5): 1473-1485, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31267347

RESUMEN

Inflammatory diseases of the central nervous system (CNS) are a diagnostic challenge to clinicians. Autoimmune encephalitis (AE) is an important diagnostic consideration in patients with CNS inflammatory disorders; despite of a wide range of neuropsychiatric symptoms it should be diagnosed as soon as possible and the patient transferred to the neurologist. We studied a group of AE patients (n = 24) as compared to multiple sclerosis (MS, n = 61) and control (n = 19) groups. Detailed clinical pictures of patients are presented. We focused on relevant cerebrospinal fluid (CSF) tests like protein levels, cytosis and oligoclonal bands, neuroinflammation indices (interleukin-6, soluble receptor of IL-6, neopterin, anti-ribosomal proteins antibodies) and markers of neurodegeneration (phosphorylated neurofilament heavy chain, pNfh). Elevated neopterin level was found in AE group as compared to the MS and control groups, while protein and pNfh were increased in both AE and MS groups. In the MS group, the cytosis and soluble receptor of IL-6 were higher as compared to the control group. Anti-ribosomal proteins antibodies were increased in a single patient with AE. High levels of protein were predictive of mortality in AE patients, while IL-6 and pNfh were elevated in severe AE patients. AE patients with paraneoplastic etiology demonstrated oligoclonal bands positivity. Taken together, our results suggest the neopterin as an additional marker of autoimmune brain inflammation. Though higher levels of protein, IL-6 and pNfh were found in patients with severe disease progression and death, prognostic values of these markers should be validated in larger cohorts of patients.


Asunto(s)
Encefalitis/metabolismo , Enfermedad de Hashimoto/metabolismo , Interleucina-6/metabolismo , Esclerosis Múltiple/metabolismo , Neopterin/metabolismo , Adolescente , Adulto , Anciano , Biomarcadores/metabolismo , Encefalitis/sangre , Encefalitis/líquido cefalorraquídeo , Femenino , Enfermedad de Hashimoto/sangre , Enfermedad de Hashimoto/líquido cefalorraquídeo , Humanos , Interleucina-6/sangre , Interleucina-6/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/líquido cefalorraquídeo , Neopterin/sangre , Neopterin/líquido cefalorraquídeo , Adulto Joven
15.
J Clin Neurosci ; 68: 281-289, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31327593

RESUMEN

Interleukin-6 (IL-6) is one of the pleiotropic cytokines and has received attention as a critical factor implicated in the invasion and the angiogenesis of various cancers. In glioma, IL-6 is known to be associated with the prognosis; however, the roles of IL-6 in cerebrospinal fluid (CSF) has not been studied sufficiently. We examined the concentration of CSF IL-6 using 75 CSF samples of glioma (54 glioblastomas (GBMs) and 21 other grades of gliomas) and analyzed the association CSF IL-6 with infiltration levels of tumor-associated macrophages (TAMs) and prognosis. The concentration of CSF IL-6 in GBM patients was significantly higher than that in other grades of gliomas. CSF IL-6 levels were associated with the infiltration rate of TAMs in GBMs, and IL-6 levels were increased in the GBM cells co-cultured with TAM-like macrophages. The CSF of GBM patients, which contained high concentration of IL-6, promoted the migration ability of GBM cells, and neutralization antibodies of IL-6 inhibited its migration ability. Finally, in both univariate and multivariate analysis, higher CSF IL-6 levels were associated with poorer prognosis in GBM patients. These results indicated that the concentration of CSF IL-6 is associated with TAMs' infiltration level and may be a useful prognostic biomarker for the GBM patients.


Asunto(s)
Biomarcadores de Tumor/líquido cefalorraquídeo , Neoplasias Encefálicas/inmunología , Glioblastoma/inmunología , Interleucina-6/líquido cefalorraquídeo , Macrófagos/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/inmunología , Neoplasias Encefálicas/líquido cefalorraquídeo , Neoplasias Encefálicas/patología , Movimiento Celular/inmunología , Femenino , Glioblastoma/líquido cefalorraquídeo , Glioblastoma/patología , Humanos , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Pronóstico , Adulto Joven
17.
Ann Clin Transl Neurol ; 6(5): 974-978, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31139696

RESUMEN

Vertebral artery dissection and recurrent meningitis are rare complications in Behçet's disease. Behçet's disease may be associated with familial Mediterranean fever. Here, we describe a 52-year-old woman with severe headache who exhibited recurrent meningitis and vertebral artery dissection. Cerebrospinal fluid showed high levels of interleukin-6. Magnetic resonance imaging revealed right vertebral artery dissection. The patient had three heterozygous mutations in the familial Mediterranean fever gene (MEFV) gene. She fulfilled criteria for diagnosis of Behçet's disease and familial Mediterranean fever. In conclusion, mutations of the MEFV gene may cause neuro-inflammatory disorders and cerebrovascular disorders by reducing anti-inflammatory activity of pyrin.


Asunto(s)
Síndrome de Behçet/complicaciones , Fiebre Mediterránea Familiar/complicaciones , Disección de la Arteria Vertebral/etiología , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Fiebre Mediterránea Familiar/genética , Femenino , Humanos , Interleucina-6/líquido cefalorraquídeo , Imagen por Resonancia Magnética , Meningitis/diagnóstico por imagen , Persona de Mediana Edad , Mutación , Pirina , Arteria Vertebral/diagnóstico por imagen , Disección de la Arteria Vertebral/diagnóstico por imagen
18.
J Coll Physicians Surg Pak ; 29(6): 528-531, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31133150

RESUMEN

OBJECTIVE: To investigate the effects of parecoxib on pain threshold and inflammatory factors interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in spinal cord of rats with bone cancer pain. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Department of Oncology, Shengjing Hospital of China Medical University, China, from March 2017 to May 2018. METHODOLOGY: Twenty-four healthy female Sprague-Dawley rats were selected and the bone cancer pain model was inoculated with W256 breast cancer cell into the bone marrow. Rats with bone cancer pain were randomly divided into the model group and the parecoxib group on the 7th day postoperation, with 12 rats in each group. Another 12 rats were taken as the control group. Rats in the parecoxib group were given intraperitoneal injection of parecoxib (8 mg/kg) for 10 consecutive days since the 15th day after operation. Mechanical pain threshold, thermal pain threshold, and the levels of inflammatory factors IL-1ß, IL-6 and TNF-α in spinal cord of rats in each group were compared. RESULTS: On the 14th postoperative day, mechanical pain threshold and thermal pain threshold of rats in the model group and the parecoxib group were significantly decreased compared with those in the control group (p<0.001). After 5 and 10 days of administration, mechanical and thermal pain threshold of rats in the parecoxib group were significantly higher than those in the model group and the control group (p<0.001). After 10 days of administration, levels of IL-1ß, IL-6 and TNF-α in spinal cord of the model group were higher than those of the control group (p<0.001); and levels of IL-1ß, IL-6 and TNF-α in spinal cord of the parecoxib group were significantly lower than those in the model group and the control group (p<0.001). CONCLUSION: Parecoxib can alleviate hyperalgesia in rats with bone cancer pain, increase pain threshold and inhibit the up-regulation of inflammatory factors in the spinal cord. Parecoxib may achieve analgesic effects by down-regulating the expression of IL-1ß, IL-6 and TNF-α in the spinal cord.


Asunto(s)
Dolor en Cáncer/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa 2/farmacología , Interleucina-1beta/efectos de los fármacos , Interleucina-6/líquido cefalorraquídeo , Isoxazoles/farmacología , Umbral del Dolor/efectos de los fármacos , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Animales , Neoplasias Óseas/patología , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Regulación hacia Abajo , Femenino , Hiperalgesia , Inflamación , Interleucina-1beta/líquido cefalorraquídeo , Isoxazoles/administración & dosificación , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Médula Espinal , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo
19.
Front Biosci (Landmark Ed) ; 24: 1158-1166, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-31136972

RESUMEN

Experimental evidence has shown that chimeric switch receptor T (CSR-T) cells, activated by binding programmed death-ligand 1 on the tumor cell surface, lead to tumor regression in experimental animals. In this phase I clinical study, we evaluated the safety and bioactivity of CSR-T cell therapy in 14 patients with recurrent glioblastoma who were unresponsive to surgical resection and standard radiotherapy. Patients who received 108 CSR-T cells either intravenously or intracranially showed an increase in the levels of IFN-gamma and IL-6, respectively, in peripheral blood or cerbrospinal fluid (CSF). Moreover, the number of T cells present in CSF significantly increased after the treatment. Patients did not show grade 3 or 4 adverse effects. The evidence of in vivo biological activity and lack of adverse effects of treatment with CSR-T cells suggest that such treatment can be subjected to further analysis to show the efficacy of this new treatment strategy in the treatment of cancers that are not responsive to traditional therapeutic regimens.


Asunto(s)
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/inmunología , Adulto , Anciano , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Femenino , Glioblastoma/inmunología , Glioblastoma/patología , Humanos , Interferón gamma/sangre , Interferón gamma/líquido cefalorraquídeo , Interferón gamma/inmunología , Interleucina-6/sangre , Interleucina-6/líquido cefalorraquídeo , Interleucina-6/inmunología , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Receptores Quiméricos de Antígenos/metabolismo , Resultado del Tratamiento
20.
Eur J Neurol ; 26(10): 1274-1280, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31021023

RESUMEN

BACKGROUND AND PURPOSE: Neurosarcoidosis is a rare inflammatory disorder of unknown cause. The aim of this study was to evaluate the value of T/B lymphocyte population counts and the concentrations of the cytokines interleukin (IL) 6 and IL-10 in the cerebrospinal fluid (CSF) of neurosarcoidosis patients. METHODS: A retrospective study CSF biomarkers was conducted in patients with neurosarcoidosis who underwent CSF analysis between 2012 and 2017 as well as various control populations. RESULTS: Forty-three patients with neurosarcoidosis, 14 with multiple sclerosis (MS) and 48 with other inflammatory disorders were analyzed. The CSF IL-6 levels were higher in sarcoidosis patients than in MS patients (median 8 vs. 3 pg/ml, P = 0.006). The CSF CD4/CD8 ratio was higher in sarcoidosis patients than in MS patients and in patients with other inflammatory disorders (median 3.18 vs. 2.36 and 2.10, respectively, P = 0.008). The CSF IL-6 level was higher in patients with active neurosarcoidosis than in non-active neurosarcoidosis patients (median 13 vs. 3 pg/ml, P = 0.0005). In patients with neurosarcoidosis, a CSF IL-6 concentration >50 pg/ml was associated with a higher risk of relapse or progression-free survival (hazard ratio 3.60; 95% confidence interval 1.78-23.14). A refractory neurosarcoidosis patient was treated with an anti-IL-6 monoclonal antibody that produced a complete neurological response. CONCLUSIONS: The CSF CD4/CD8 ratio and IL-6 concentration are increased in neurosarcoidosis compared to MS and other inflammatory disorders. A CSF IL-6 concentration >50 pg/ml is associated with relapse or progression of neurosarcoidosis. IL-10 levels may be elevated in neurosarcoidosis.


Asunto(s)
Relación CD4-CD8 , Enfermedades del Sistema Nervioso Central/líquido cefalorraquídeo , Líquido Cefalorraquídeo/citología , Interleucina-10/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Sarcoidosis/líquido cefalorraquídeo , Adulto , Biomarcadores/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso Central/inmunología , Femenino , Humanos , Inflamación/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/líquido cefalorraquídeo , Supervivencia sin Progresión , Recurrencia , Estudios Retrospectivos , Sarcoidosis/inmunología , Resultado del Tratamiento , Adulto Joven
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