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1.
Muscle Nerve ; 62(4): 528-533, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32696574

RESUMEN

INTRODUCTION: Evidence-based information about cerebrospinal fluid (CSF) levels of biomarkers in patients with amyotrophic lateral sclerosis (ALS) is limited. METHODS: Vascular endothelial growth factor (VEGF) and its receptor vascular endothelial growth factor receptor 2 (VEGFR2), optineurin (OPTN), monocyte chemoattractant protein-1 (MCP-1), angiogenin (ANG), and TAR DNA-binding protein (TDP-43) were quantified by enzyme-linked immunoassay in the CSF of 54 patients with sporadic ALS and 32 controls in a case-control study design. RESULTS: CSF levels of VEGF (P = .014) and ANG (P = .009) were decreased, whereas VEGFR2 was higher (P = .002) in patients with ALS than in controls. TDP-43 positively correlated with MCP-1 (P = .003), VEGF (P < .001), and VEGFR2 (P < .001) in patients with ALS. DISCUSSION: Our findings suggest possible utility of VEGF, VEGFR2, and ANG as biomarkers for use in ALS treatment trials.


Asunto(s)
Esclerosis Amiotrófica Lateral/diagnóstico , Proteínas de Ciclo Celular/líquido cefalorraquídeo , Quimiocina CCL2/líquido cefalorraquídeo , Proteínas de Unión al ADN/líquido cefalorraquídeo , Proteínas de Transporte de Membrana/líquido cefalorraquídeo , Ribonucleasa Pancreática/líquido cefalorraquídeo , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Adulto , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Femenino , Humanos , India , Masculino , Persona de Mediana Edad
2.
J Neurooncol ; 145(2): 233-239, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31624989

RESUMEN

INTRODUCTION: Gliomas are tumors of the central nervous system. Despite new classifications, they are still divided in low and high-grade gliomas, being the latter of greater malignancy. The degree of malignancy is directly related with the angiogenic activity in tumoral tissues. We measured VEGF concentrations and angiogenic capacity in cerebrospinal fluid (CSF) from patients with high and low-grade gliomas. The purpose of this study was to find a biomarker that contributes in the differential diagnosis and prognosis of gliomas. METHODS: CSF was obtained from 19 individuals: 8 with low-grade gliomas, 6 with high-grade gliomas and 5 controls. VEGF concentration in CSF was measured by ELISA and the angiogenic capacity was measured by chick chorioallantoic membrane (CAM) test. RESULTS: The VEGF concentration was higher in patients with high-grade gliomas, compared to patients with low-grade gliomas and controls (2860 pg/mL ± 975 vs. 182.6 ± 37.1 and 47.4 ± 0.4, respectively). On the other hand, CSF from patients with high-grade gliomas generated a higher microvascular density (MVD) than patients with low-grade gliomas and controls (13.23 ± 0.6 vessels/9000µm2 vs. 9.3 ± 0.3 and 7.92 ± 0.2, respectively). Interestingly, there was not statistical differences in both VEGF levels and angiogenic capacity in patients with low-grade gliomas and controls. CONCLUSION: Together VEGF levels and angiogenic capacity in CSF can be used as a biological marker of gliomas malignancy.


Asunto(s)
Neoplasias Encefálicas/diagnóstico , Glioma/diagnóstico , Neovascularización Patológica , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Neoplasias Encefálicas/líquido cefalorraquídeo , Neoplasias Encefálicas/fisiopatología , Glioma/líquido cefalorraquídeo , Glioma/fisiopatología , Humanos , Proyectos Piloto , Pronóstico
3.
J Affect Disord ; 253: 449-453, 2019 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-31103810

RESUMEN

BACKGROUND: Several lines of evidence are pointing towards an involvement of the vascular endothelial growth factor (VEGF) in the pathophysiology of depression. There are studies analyzing blood levels of VEGF in patients with depression compared to controls, but a data on cerebrospinal fluid (CSF) levels of VEGF in patients with depression are lacking. METHOD: CSF VEGF levels were measured in patients (n = 12) with a severe, treatment-resistant depressive episode before and after the antidepressant treatment by a course of electroconvulsive therapy (ECT) and compared to age- and sex-matched controls (n = 20). RESULTS: The patients with depression showed lower mean VEGF levels in the CSF prior to ECT than the controls (p = 0.041). Regarding the patients, CSF VEGF concentration at baseline and after the complete ECT treatment did not differ from each other (p = 0.78). LIMITATIONS: Major limitations of this study are the small sample size and that data from corresponding serum levels cannot be provided. Another limitation is that the controls were not completely healthy, as they were recruited from a memory clinic with subjective complaints. The timing of the second sample might have been suboptimal, when taking into account that there might be an on-going phase of re-equilibrating after ECT. CONCLUSIONS: CSF VEGF concentrations were lower in a clinical sample of patients with treatment-resistant depression compared with matched controls. Additionally, no change in CSF VEGF levels during a course of ECT could be detected.


Asunto(s)
Trastorno Depresivo Mayor/líquido cefalorraquídeo , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Resistente al Tratamiento/líquido cefalorraquídeo , Trastorno Depresivo Resistente al Tratamiento/terapia , Terapia Electroconvulsiva , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Adulto , Antidepresivos , Depresión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto
4.
J Neuroinflammation ; 16(1): 7, 2019 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-30626412

RESUMEN

BACKGROUND: Cerebrospinal fluid (CSF) shunt placement is frequently complicated by bacterial infection. Shunt infection diagnosis relies on bacterial culture of CSF which can often produce false-negative results. Negative cultures present a conundrum for physicians as they are left to rely on other CSF indices, which can be unremarkable. New methods are needed to swiftly and accurately diagnose shunt infections. CSF chemokines and cytokines may prove useful as diagnostic biomarkers. The objective of this study was to evaluate the potential of systemic and CSF biomarkers for identification of CSF shunt infection. METHODS: We conducted a retrospective chart review of children with culture-confirmed CSF shunt infection at Children's Hospital and Medical Center from July 2013 to December 2015. CSF cytokine analysis was performed for those patients with CSF in frozen storage from the same sample that was used for diagnostic culture. RESULTS: A total of 12 infections were included in this study. Patients with shunt infection had a median C-reactive protein (CRP) of 18.25 mg/dL. Median peripheral white blood cell count was 15.53 × 103 cells/mL. Those with shunt infection had a median CSF WBC of 332 cells/mL, median CSF protein level of 406 mg/dL, and median CSF glucose of 35.5 mg/dL. An interesting trend was observed with gram-positive infections having higher levels of the anti-inflammatory cytokine interleukin (IL)-10 as well as IL-17A and vascular endothelial growth factor (VEGF) compared to gram-negative infections, although these differences did not reach statistical significance. Conversely, gram-negative infections displayed higher levels of the pro-inflammatory cytokines IL-1ß, fractalkine (CX3CL1), chemokine ligand 2 (CCL2), and chemokine ligand 3 (CCL3), although again these were not significantly different. CSF from gram-positive and gram-negative shunt infections had similar levels of interferon gamma (INF-γ), tumor necrosis factor alpha (TNF-α), IL-6, and IL-8. CONCLUSIONS: This pilot study is the first to characterize the CSF cytokine profile in patients with CSF shunt infection and supports the distinction of chemokine and cytokine profiles between gram-negative and gram-positive infections. Additionally, it demonstrates the potential of CSF chemokines and cytokines as biomarkers for the diagnosis of shunt infection.


Asunto(s)
Citocinas/líquido cefalorraquídeo , Infecciones por Bacterias Gramnegativas/líquido cefalorraquídeo , Infecciones por Bacterias Grampositivas/líquido cefalorraquídeo , Adolescente , Proteína C-Reactiva/líquido cefalorraquídeo , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Adulto Joven
5.
Front Immunol ; 9: 2122, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30283455

RESUMEN

It has been suggested that cytokine-mediated inflammation plays a key role for the onset and/or development of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). However, clinical studies have yielded inconsistent results for the aberrant cytokine levels in circulation of patients with AD, PD, and ALS. Previous studies have used meta-analysis to address the inconsistent data for blood cytokine levels in the patients with AD, PD, and ALS. Here, we performed a systemic review of cerebrospinal fluid inflammatory cytokine data in patients with AD, PD and ALS, and sought to quantitatively summarize the CSF inflammatory cytokine data with a meta-analytical technique. The systematic search from Pubmed and Web of Science identified 71 articles with 2629 patients and 2049 controls for the meta-analysis. Random-effects meta-analysis demonstrated that CSF TGF-ß, MCP-1, and YKL-40 levels were significantly elevated in AD patients when compared with controls. In addition, patients with PD had heightened levels of TGF-ß1, IL-6, and IL-1ß in CSF. Furthermore, G-CSF, IL-2, IL-15, IL-17, MCP-1, MIP-1α, TNF-α, and VEGF levels were significantly increased in patients with ALS as compared with controls. Taken together, these results not only strengthen the clinical evidence that neurodegenerative diseases are accompanied by the increased inflammatory response, but also reveal the unique inflammatory response profile in the central nervous system of patients with AD, PD and ALS. Given the robust associations between some cytokines and neurodegenerative diseases found in this meta-analysis, CSF inflammatory cytokines may be used as biomarkers for these diseases in the future.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Esclerosis Amiotrófica Lateral/líquido cefalorraquídeo , Citocinas/líquido cefalorraquídeo , Mediadores de Inflamación/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico , Esclerosis Amiotrófica Lateral/diagnóstico , Biomarcadores/líquido cefalorraquídeo , Sistema Nervioso Central/metabolismo , Humanos , Enfermedad de Parkinson/líquido cefalorraquídeo , Enfermedad de Parkinson/diagnóstico , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo
6.
Neurosci Lett ; 687: 276-279, 2018 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-30278247

RESUMEN

The association of vascular endothelial growth factor (VEGF) levels in CSF and cerebral glucose metabolism across the Alzheimer's disease (AD) spectrum is unclear. CSF VEGF levels were cross-sectionally related to cerebral glucose metabolism, as measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET), using linear regression models. We found that VEGF levels were associated with cerebral glucose metabolism in patients with mild cognitive impairment (MCI) and AD, but not in cognitively normal older adults. Our data indicated that VEGF may play an important role in cerebral glucose metabolism.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Glucosa/líquido cefalorraquídeo , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/líquido cefalorraquídeo , Disfunción Cognitiva/metabolismo , Femenino , Fluorodesoxiglucosa F18/metabolismo , Humanos , Masculino , Tomografía de Emisión de Positrones/métodos , Radiofármacos/líquido cefalorraquídeo , Radiofármacos/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
7.
Alzheimers Res Ther ; 10(1): 58, 2018 06 23.
Artículo en Inglés | MEDLINE | ID: mdl-29933741

RESUMEN

BACKGROUND: Increasing evidence suggests that cerebral vascular dysfunction is associated with the early stages of Alzheimer's disease (AD). Vascular endothelial growth factor (VEGF) is one of the key players involved in the development and maintenance of the vasculature. Here, we hypothesized that VEGF levels in cerebrospinal fluid (CSF) may be altered in AD patients with vascular involvement, characterized by the presence of microbleeds (MB), and in vascular dementia (VaD) patients compared to controls. METHODS: VEGF levels were determined by electrochemilumiscence Meso Scale Discovery (MULTI-SPOT Assay System) in CSF from age-matched groups of controls with subjective cognitive decline (n = 21), AD without MB (n = 25), AD with MB (n = 25), and VaD (n = 21) patients. RESULTS: The average level of VEGF in the different groups was 2.8 ± 1 pg/ml CSF. Adjusted for age and gender, no significant differences were detected between groups (p > 0.5). However, we detected a significant correlation between the concentration of VEGF in the CSF and age (r = 0.22, p = 0.03). In addition, males (n = 54) revealed higher VEGF levels in their CSF compared to females (n = 38) (males = 3.08 ± 0.769 pg/ml (mean ± SD), females = 2.6 ± 0.59; p = 0.006), indicating a gender-related regulation. CONCLUSION: Our study suggests that VEGF levels in the CSF do not reflect the cerebral vascular alterations in either AD or VaD patients. The observed associations of VEGF with age and gender may indicate that VEGF reflects normal aging and that males and females may differ in their aging process.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Demencia Vascular/líquido cefalorraquídeo , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/diagnóstico por imagen , Trastornos del Conocimiento/etiología , Estudios de Cohortes , Correlación de Datos , Demencia Vascular/complicaciones , Demencia Vascular/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad
8.
Alzheimers Res Ther ; 10(1): 25, 2018 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-29482610

RESUMEN

BACKGROUND: Neuroinflammation has gained increasing attention as a potential contributing factor in Alzheimer's disease (AD) pathology. A clinical cerebrospinal fluid biomarker capable of monitoring this process during the course of the disease has yet to emerge, chiefly owing to contradictory research findings. In this study, we sought to clarify the utility of inflammatory biomarkers in diagnostic procedures of AD in three steps: (1) to screen for proteins that are robustly detectable in cerebrospinal fluid; (2) based on this analysis, to explore any associations between the analytically robust markers and salient pathological features of AD; and (3) to determine the discriminative power of these markers in the clinical diagnosis of AD. METHODS: From a total of 46 proteins, 15 that were robustly detectable in cerebrospinal fluid were identified. A subsequent analysis of these markers in a cohort of 399 patients (nondemented subjects, patients with mild cognitive impairment [MCI], and patients with AD, supplemented by smaller cohorts of other diseases) was conducted. Fluid biomarker data were related to AD pathology and neuropsychological markers and adjusted for confounders such as age, sex, apolipoprotein E genotype, and biobank storage time. RESULTS: Cerebrospinal fluid levels of C-reactive protein and soluble TREM2 differed between nondemented subjects, patients with MCI, or patients with AD and were associated with amyloid and tau pathology. Several markers were associated with tau pathology only or with other neurodegenerative diseases. Correlations between neuropsychological performance and inflammatory markers were weak, but they were most prominent in AD and for the most challenging cognitive tests. All investigated covariates had significant influence, with varying effects across the markers. Still, none of the markers achieved discriminative power of more than 70% to distinguish between patient groups defined by clinical or neuropathological categories. CONCLUSIONS: Basic analytical considerations proved indispensable for this type of study because only one-third of the tested markers were robustly detectable in cerebrospinal fluid. Detectable inflammatory protein markers were associated in multiple ways with AD pathology. Yet, even significantly associated markers were not powerful enough in terms of effect strength, sensitivity, and specificity, and hence they were not suited for direct use in clinical diagnostic practice. Targets other than those most commonly considered in this field of research might provide results with better clinical applicability.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Proteína C-Reactiva/líquido cefalorraquídeo , Proteínas del Líquido Cefalorraquídeo/líquido cefalorraquídeo , Citocinas/líquido cefalorraquídeo , Glicoproteínas de Membrana/líquido cefalorraquídeo , Adulto , Anciano , Anciano de 80 o más Años , Péptidos beta-Amiloides/líquido cefalorraquídeo , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Receptores Inmunológicos , Estadísticas no Paramétricas , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo
9.
J Neuroinflammation ; 14(1): 193, 2017 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-28962579

RESUMEN

BACKGROUND: Surgery and anesthesia have been linked to postoperative cognitive disturbance and increased risk of Alzheimer's disease. It is not clear by which mechanisms this increased risk for cognitive disease is mediated. Further, amyloid ß production has been suggested to depend on the sleep-wake cycle and neuronal activity. The aim of the present study was to examine if cerebrospinal fluid (CSF) concentrations of a number of biomarkers for Alzheimer's disease-related processes, including amyloid ß, neuronal injury, and inflammation, changed over time during intravenous anesthesia in surgical patients. METHODS: We included patients scheduled for hysterectomy via laparotomy during general anesthesia with intravenous propofol and remifentanil. CSF samples were obtained before, during, and after surgery (5 h after induction) and tested for 27 biomarkers. Changes over time were tested with linear mixed effects models. RESULTS: A total of 22 patients, all females, were included. The mean age was 50 years (± 9 SD). The mean duration of the anesthesia was 145 min (± 40 SD). Interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, and vascular endothelial growth factor A increased over time. IL-15 and IL-7 decreased slightly over time. Macrophage inflammatory protein 1ß and placental growth factor also changed significantly. There were no significant effects on amyloid ß (Aß) or tau biomarkers. CONCLUSIONS: Surgery and general anesthesia with intravenous propofol and remifentanil induce, during and in the short term after the procedure, a neuroinflammatory response which is dominated by monocyte attractants, without biomarker signs of the effects on Alzheimer's disease pathology or neuronal injury.


Asunto(s)
Enfermedad de Alzheimer , Biomarcadores/líquido cefalorraquídeo , Inflamación/líquido cefalorraquídeo , Piperidinas/uso terapéutico , Propofol/uso terapéutico , Adulto , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/cirugía , Péptidos beta-Amiloides/líquido cefalorraquídeo , Anestesia Intravenosa/métodos , Estudios de Cohortes , Citocinas/líquido cefalorraquídeo , Femenino , Humanos , Persona de Mediana Edad , Fragmentos de Péptidos/líquido cefalorraquídeo , Remifentanilo , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo
10.
Neurobiol Aging ; 51: 104-112, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28061383

RESUMEN

Blood-brain barrier (BBB) dysfunction might be an important component of many neurodegenerative disorders. In this study, we investigated its role in dementia using large clinical cohorts. The cerebrospinal fluid (CSF)/plasma albumin ratio (Qalb), an indicator of BBB (and blood-CSF barrier) permeability, was measured in a total of 1015 individuals. The ratio was increased in patients with Alzheimer's disease, dementia with Lewy bodies or Parkinson's disease dementia, subcortical vascular dementia, and frontotemporal dementia compared with controls. However, this measure was not changed during preclinical or prodromal Alzheimer's disease and was not associated with amyloid positron emission tomography or APOE genotype. The Qalb was increased in diabetes mellitus and correlated positively with CSF biomarkers of angiogenesis and endothelial dysfunction (vascular endothelial growth factor, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1). In healthy elderly, high body mass index and waist-hip ratio predicted increased Qalb 20 years later. In summary, BBB permeability is increased in major dementia disorders but does not relate to amyloid pathology or APOE genotype. Instead, BBB impairment may be associated with diabetes and brain microvascular damage.


Asunto(s)
Barrera Hematoencefálica/fisiopatología , Permeabilidad Capilar , Demencia/etiología , Diabetes Mellitus/etiología , Anciano , Anciano de 80 o más Años , Albúminas/líquido cefalorraquídeo , Péptidos beta-Amiloides/metabolismo , Apolipoproteínas E/genética , Molécula 1 de Adhesión Celular , Moléculas de Adhesión Celular/líquido cefalorraquídeo , Estudios de Cohortes , Diabetes Mellitus/sangre , Diabetes Mellitus/líquido cefalorraquídeo , Femenino , Genotipo , Humanos , Inmunoglobulinas/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Albúmina Sérica , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo
11.
Transl Psychiatry ; 7(1): e995, 2017 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-28072416

RESUMEN

Brain autopsy and biomarker studies indicate that the pathology of Alzheimer's disease (AD) is initiated at least 10-20 years before clinical symptoms. This provides a window of opportunity to initiate preventive treatment. However, this emphasizes the necessity for biomarkers that identify individuals at risk for developing AD later in life. In this cross-sectional study, originating from three epidemiologic studies in Sweden (n=1428), the objective was to examine whether amyloid pathology, as determined by low cerebrospinal fluid (CSF) concentration of the 42 amino acid form of ß-amyloid (Aß42), is associated with biomarker evidence of other pathological changes in cognitively healthy elderly. A total of 129 patients were included and CSF levels of Aß42, total tau, tau phosphorylated at threonine 181 (p-tau), neurogranin, VILIP-1, VEGF, FABP3, Aß40, neurofilament light, MBP, orexin A, BDNF and YKL-40 were measured. Among these healthy elderly, 35.6% (N=46) had CSF Aß42 levels below 530 pg ml-1. These individuals displayed significantly higher CSF concentrations of t-tau (P<0.001), p-tau (181) (P<0.001), neurogranin (P=0.009) and FABP3 (P=0.044) compared with amyloid-negative individuals. Our study indicates that there is a subpopulation among healthy older individuals who have amyloid pathology along with signs of ongoing neuronal and synaptic degeneration, as well as tangle pathology. Previous studies have demonstrated that increase in CSF tau and p-tau is a specific sign of AD progression that occurs downstream of the deposition of Aß. On the basis of this, our data suggest that these subjects are at risk for developing AD. We also confirm the association between APOE ɛ4 and amyloid pathology in healthy older individuals.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/líquido cefalorraquídeo , Apolipoproteína E4/genética , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Proteína 1 Similar a Quitinasa-3/líquido cefalorraquídeo , Estudios Transversales , Proteína 3 de Unión a Ácidos Grasos/líquido cefalorraquídeo , Femenino , Voluntarios Sanos , Humanos , Masculino , Proteína Básica de Mielina/líquido cefalorraquídeo , Neurocalcina/líquido cefalorraquídeo , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Neurogranina/líquido cefalorraquídeo , Orexinas/líquido cefalorraquídeo , Fragmentos de Péptidos/líquido cefalorraquídeo , Fosfoproteínas/líquido cefalorraquídeo , Suecia , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo
13.
Turk Neurosurg ; 27(1): 53-59, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27593764

RESUMEN

AIM: The purpose of this study was to investigate whether the intensity of trauma influences the pathogenesis of traumatic chronic subdural hematoma (CSDH). MATERIAL AND METHODS: Thirty-one patients treated surgically for traumatic CSDH were divided into high-impact and lowimpact groups according to the intensity of trauma. They were respectively evaluated with respect to clinical and radiological findings at presentation, and the subdural concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor, and beta-trace protein (ΒTP) [a highly specific protein in the cerebrospinal fluid (CSF)] related to the pathogenesis of CSDH. If ΒTP (subdural fluid/serum) was > 2, an admixture of CSF to the subdural fluid was indicated. RESULTS: The ΒTP (subdural fluid/serum) was > 2 in all patients with a traumatic CSDH. The mean concentration of subdural ΒTP in the high-impact group was higher than in the low-impact group (6.1 mg/L versus 3.9 mg/L), and the difference was statistically significant (p=0.02). In addition, mean concentrations of IL-6, IL-8 and VEGF were higher in the high-impact group, as compared to the low-impact group, though the differences did not reach statistical significance. CONCLUSION: Trauma may be related to CSF leakage into the subdural space in CSDH, and the intensity of trauma may influence the amount of CSF leakage. Although there is no direct correlation between the amount of CSF leakage and other subdural molecules, the intensity of trauma may be associated with larger concentrations of molecules in traumatic CSDH.


Asunto(s)
Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/patología , Hematoma Subdural Crónico/complicaciones , Hematoma Subdural Crónico/patología , Adulto , Anciano , Lesiones Traumáticas del Encéfalo/líquido cefalorraquídeo , Pérdida de Líquido Cefalorraquídeo/complicaciones , Femenino , Factor 2 de Crecimiento de Fibroblastos/líquido cefalorraquídeo , Hematoma Subdural Crónico/líquido cefalorraquídeo , Humanos , Interleucina-6/líquido cefalorraquídeo , Interleucina-8/líquido cefalorraquídeo , Oxidorreductasas Intramoleculares/líquido cefalorraquídeo , Lipocalinas/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo
14.
J Infect Chemother ; 23(2): 80-84, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27887787

RESUMEN

INTRODUCTION: To search for an index of neurologic prognosis of children with influenza-associated encephalopathy (IAE), involvement of angiogenesis-related growth factors in the pathology was investigated. PATIENTS AND METHODS: The subjects were 11 IAE patients, 6 patients with bacterial meningitis (BM), and 24 patients with non-central nervous system infection as a control group admitted to our hospital. The correlation between the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) levels in cerebrospinal fluid and the relationship with an index of inflammatory marker, interleukin (IL)-6, were investigated. Using the Pediatric Cerebral Performance Categories (PCPC) score as a prognostic indicator, we evaluated the association between the biomarkers and neurologic prognosis. RESULT: PDGF significantly increased in the IAE group compared with that in the BM group. Cerebrospinal fluid VEGF and PDGF increased in all IAE and BM patients compared with that in the control group, and VEGF and PDGF were positively correlated in the 2 groups. No correlation was found between the cerebrospinal fluid VEGF and PDGF levels and IL-6 level in the IAE group, whereas a correlation was found in the BM group. All these factors increased in patients with poor neurologic prognosis. DISCUSSION: It is possible that the disease state of IAE can be evaluated based on vascular endothelial disorder-related markers.


Asunto(s)
Encefalitis Viral/líquido cefalorraquídeo , Gripe Humana/líquido cefalorraquídeo , Meningitis Bacterianas/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Preescolar , Encefalitis Viral/complicaciones , Femenino , Humanos , Lactante , Gripe Humana/complicaciones , Interleucina-6/líquido cefalorraquídeo , Masculino , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas
15.
Neonatology ; 111(3): 253-259, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27902983

RESUMEN

BACKGROUND: Infants with neonatal encephalopathy (NE) of hypoxic-ischaemic origin are at risk of oxidative and ischaemia-reperfusion injury, which may induce abnormal inflammatory responses involving excessive cytokine production and release in serum and cerebrospinal fluid (CSF). Systemic inflammation is found in infants with NE, and we therefore were interested in cytokines associated with hypoxia, including vascular endothelial growth factor (VEGF) and erythropoietin (Epo). OBJECTIVE: To investigate the relationship between Epo, VEGF levels, brain injury and outcome in a group of term infants exposed to perinatal asphyxia (PA) compared to controls. METHODS: Serum and CSF biomarkers associated with hypoxia (VEGF, Epo) were serially measured using multiplex immunoassays over days 1-4 in term infants exposed to PA including infants with NE and controls. Results were compared to severity of encephalopathy, MR brain imaging and mortality. RESULTS: Ninety-four infants had 247 serum samples collected (n = 12 controls, 82 exposed to PA with 34 CSF samples), and 4 infants died. Controls had significantly lower serum Epo levels on days 1 and 2 compared to those exposed to PA (p = 0.02). Grade II/III NE was significantly associated with elevated day 2 Epo and decreased day 1 VEGF (p < 0.05; day 2 Epo AUC = 0.74, cut-off 10.05 IU/ml). Elevated serum Epo was associated with severely abnormal MRI. Mortality was associated with elevated day 3 Epo and decreased day 1 VEGF. CSF levels were all after hypothermia and were not significantly associated with outcome. CONCLUSION: Serum Epo and VEGF may be markers of severity of hypoxia-ischaemia and brain injury as they are closely related to hypoxic exposure.


Asunto(s)
Asfixia Neonatal/complicaciones , Encéfalo/diagnóstico por imagen , Eritropoyetina/sangre , Hipoxia-Isquemia Encefálica/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Eritropoyetina/líquido cefalorraquídeo , Femenino , Humanos , Hipoxia-Isquemia Encefálica/líquido cefalorraquídeo , Hipoxia-Isquemia Encefálica/diagnóstico por imagen , Recién Nacido , Irlanda , Imagen por Resonancia Magnética , Masculino , Índice de Severidad de la Enfermedad , Centros de Atención Terciaria , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo
16.
Neurochem Res ; 41(7): 1713-22, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27084769

RESUMEN

Idiopathic normal pressure hydrocephalus is a neurological disease caused by abnormal cerebrospinal fluid flow and presents with symptoms such as dementia. Current therapy involves the removal of excess cerebrospinal fluid by shunting. Not all patients respond to this therapy and biomarkers are needed that could facilitate the characterization of patients likely to benefit from this treatment. Here, we measure brain metabolism in normal pressure hydrocephalus patients by performing a novel longitudinal metabolomic profiling study of cerebrospinal fluid. We find that the levels of brain metabolites correlate with clinical parameters, the amount of vascular endothelial growth factor in the cerebrospinal fluid, and environmental stimuli such as exercise. Metabolomic analysis of normal pressure hydrocephalus patients provides insight into changes in brain metabolism that accompany cerebrospinal fluid disorders and may facilitate the development of new biomarkers for this condition.


Asunto(s)
Ejercicio Físico/fisiología , Hidrocéfalo Normotenso/líquido cefalorraquídeo , Metabolómica/métodos , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Anciano , Biomarcadores/líquido cefalorraquídeo , Femenino , Humanos , Hidrocéfalo Normotenso/metabolismo , Estudios Longitudinales , Masculino , Metabolómica/tendencias , Resultado del Tratamiento
17.
Hematol Oncol ; 34(1): 36-41, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25312095

RESUMEN

Burkitt's lymphoma (BL) is a malignancy of B lymphocytes. The rapid growth rate and frequent systemic spread result in most patients presenting with advanced disease at diagnosis. Cerebrospinal fluid cytology is the gold standard (with very high accuracy) for diagnosing BL central nervous system (CNS) metastasis; however, the low sensitivity of this method limits its clinical applications. Here, we report a case of BL with CNS metastasis. The levels of vascular endothelial growth factor (VEGF)-A and VEGF-C in the serum and cerebrospinal fluid were used to evaluate the status of BL remission and recurrence. Comparisons were made between VEGF and the other risk factors used in evaluating CNS metastasis. Although not in strict accordance, VEGF levels mirrored the disease course. Therefore, VEGF may reflect the status of BL CNS metastasis. Understanding the role of VEGF in CNS metastasis may help to improve the staging and risk classification of BL as well as the investigation of targeted therapy.


Asunto(s)
Encéfalo/patología , Linfoma de Burkitt/patología , Invasividad Neoplásica/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/líquido cefalorraquídeo , Linfoma de Burkitt/sangre , Linfoma de Burkitt/líquido cefalorraquídeo , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/epidemiología , Líquido Cefalorraquídeo/citología , Diplopía/etiología , Femenino , Cefalea/etiología , Humanos , Inmunofenotipificación , Ganglios Linfáticos/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Neovascularización Patológica/sangre , Neovascularización Patológica/líquido cefalorraquídeo , Recurrencia , Factores de Riesgo , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Factor C de Crecimiento Endotelial Vascular/sangre , Factor C de Crecimiento Endotelial Vascular/líquido cefalorraquídeo
18.
J Clin Neurosci ; 24: 52-6, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26498093

RESUMEN

Vascular endothelial growth factor (VEGF) is a growth factor demonstrated to be a key factor in cerebral angiogenesis and neurogenesis. It has been considered a critical component in hippocampus neurogenesis and memory formation and has been observed to increase in the rat hippocampus after exercise. We previously found increased VEGF levels in experimental chronic hydrocephalus in several brain areas and cerebrospinal fluid (CSF), suggesting a role in the adaption to chronic hypoxia. Here we investigate the ability of moderate exercise to increase CSF-VEGF levels in adult chronic hydrocephalus patients. Lumbar CSF samples were collected from 17 normal pressure hydrocephalus patients. During CSF collection, 11 patients (exercise group) underwent a standard in-room occupational therapy session; six patients (no-exercise group) did not undergo a physical therapy session. CSF-VEGF levels were evaluated for increase related to exercise and the clinical response to CSF drainage. CSF-VEGF levels in the exercise group demonstrated significant increases 1-3 hours post-exercise compared with the levels 1-2 hours pre-exercise (p=0.04), and also showed significantly higher levels than the no-exercise groups (p=0.03). The post-exercise CSF-VEGF level in the group that did not clinically improve was significantly higher than both their own pre-exercise level (p=0.02) and that seen in the clinically improving group (p=0.05) after exercise. We conclude that CSF-VEGF levels can increase after moderate exercise even in elderly hydrocephalus patients. This suggests that a potential benefit of exercise, especially in CSF drainage non-improved patients, may exist via a central VEGF mechanism.


Asunto(s)
Terapia por Ejercicio/métodos , Hidrocéfalo Normotenso/líquido cefalorraquídeo , Hidrocéfalo Normotenso/rehabilitación , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo , Adulto , Anciano , Femenino , Humanos , Masculino
19.
Genet Mol Res ; 14(3): 8725-32, 2015 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-26345804

RESUMEN

We aimed to evaluate the levels of growth factors in the cerebrospinal fluid (CSF) of patients with autism after transplantation of umbilical cord blood mononuclear cells (CBMNCs). Fourteen subjects diagnosed with autism received transplantation of CBMNCs first through intravenous infusion, and three times subsequently through intrathecal injections. A 2-mL sample of CSF was taken before each intrathecal injection. CSF levels of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) were determined by enzyme-linked immunosorbent assay. All data are reported as means ± SD and were analyzed using the SPSS 10.0 software. One-way analysis of variance with post-hoc F-and Q-tests were performed for comparisons. NGF levels in the CSF were significantly increased after transplantation (213.54 ± 56.38 after the third versus 28.32 ± 12.22 ng/L after the first transplantation; P < 0.05), while VEGF and bFGF levels did not change significantly. Therefore, transplantation of CBMNCs could increase NGF levels in the CSF of patients with autism.


Asunto(s)
Trastorno Autístico/líquido cefalorraquídeo , Sangre Fetal/citología , Leucocitos Mononucleares/trasplante , Factor de Crecimiento Nervioso/líquido cefalorraquídeo , Trastorno Autístico/terapia , Niño , Preescolar , Femenino , Factor 2 de Crecimiento de Fibroblastos/líquido cefalorraquídeo , Humanos , Masculino , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/líquido cefalorraquídeo
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