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1.
Anal Chem ; 91(9): 5654-5659, 2019 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-30888153

RESUMEN

Single particle collision is emerging as a powerful and sensitive technique for analyzing small molecules, however, its application in biomacromolecules detection, for example, protein, in complex biological environments is still challenging. Here, we present the first demonstration on the single particle collision that can be developed for the detection of platelet-derived growth factor (PDGF), an important protein involved in the central nervous system in living rat brain. The system features Pt nanoparticles (PtNPs) conjugated with the PDGF recognition aptamer, suppressing the electrocatalytic collision of PtNPs toward the oxidation of hydrazine. In the presence of PDGF, the stronger binding between targeted protein and the aptamer disrupts the aptamer/PtNPs conjugates, recovering the electrocatalytic performance of PtNPs, and allowing quantitative, selective, and highly sensitive detection of PDGF in cerebrospinal fluid of rat brain.


Asunto(s)
Aptámeros de Nucleótidos/química , Encéfalo/metabolismo , Nanopartículas del Metal/química , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Platino (Metal)/química , Animales , Técnicas Biosensibles , Masculino , Oxidación-Reducción , Ratas , Ratas Sprague-Dawley
2.
Neurochem Res ; 44(3): 726-733, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29392518

RESUMEN

Maintenance of synaptic plasticity reserve is crucial to contrast clinical deterioration in MS and PDGF plays a key role in this phenomenon. Indeed, higher cerebrospinal fluid PDGF concentration correlates with improved clinical recovery after a relapse, and the amplitude of LTP-like cortical plasticity in relapsing-remitting MS patients. However, LTP-like cortical plasticity varies depending on the individual level of inhibitory cortical circuits. Aim of this study was to explore whether PDGF-CSF concentration correlates with inhibitory cortical circuits explored by means of transcranial magnetic stimulation in patients affected by relapsing-remitting MS. We further performed electrophysiological experiments evaluating GABAergic transmission in the experimental autoimmune encephalomyelitis (EAE) hippocampus. Our results reveal that increased CSF PDGF concentration correlates with decreased short afferent inhibition in the motor cortex in MS patients and decreased GABAergic activity in EAE. These findings show that PDGF affects GABAergic activity both in MS patients and in EAE hippocampus.


Asunto(s)
Potenciación a Largo Plazo/fisiología , Memoria/fisiología , Esclerosis Múltiple/líquido cefalorraquídeo , Plasticidad Neuronal/fisiología , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Adulto , Estimulación Eléctrica/métodos , Encefalomielitis Autoinmune Experimental/fisiopatología , Femenino , Hipocampo/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/fisiopatología , Estimulación Magnética Transcraneal/métodos , Adulto Joven
3.
J Neuroinflammation ; 15(1): 108, 2018 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-29655371

RESUMEN

BACKGROUND: In the early phases of relapsing-remitting multiple sclerosis (RR-MS), a clear correlation between brain lesion load and clinical disability is often lacking, originating the so-called clinico-radiological paradox. Different factors may contribute to such discrepancy. In particular, synaptic plasticity may reduce the clinical expression of brain damage producing enduring enhancement of synaptic strength largely dependent on neurotrophin-induced protein synthesis. Cytokines released by the immune cells during acute inflammation can alter synaptic transmission and plasticity possibly influencing the clinical course of MS. In addition, immune cells may promote brain repair during the post-acute phases, by secreting different growth factors involved in neuronal and oligodendroglial cell survival. Platelet-derived growth factor (PDGF) is a neurotrophic factor that could be particularly involved in clinical recovery. Indeed, PDGF promotes long-term potentiation of synaptic activity in vitro and in MS and could therefore represent a key factor improving the clinical compensation of new brain lesions. The aim of the present study is to explore whether cerebrospinal fluid (CSF) PDGF concentrations at the time of diagnosis may influence the clinical course of RR-MS. METHODS: At the time of diagnosis, we measured in 100 consecutive early MS patients the CSF concentrations of PDGF, of the main pro- and anti-inflammatory cytokines, and of reliable markers of neuronal damage. Clinical and radiological parameters of disease activity were prospectively collected during follow-up. RESULTS: CSF PDGF levels were positively correlated with prolonged relapse-free survival. Radiological markers of disease activity, biochemical markers of neuronal damage, and clinical parameters of disease progression were instead not influenced by PDGF concentrations. Higher CSF PDGF levels were associated with an anti-inflammatory milieu within the central nervous system. CONCLUSIONS: Our results suggest that PDGF could promote a more prolonged relapse-free period during the course of RR-MS, without influencing inflammation reactivation and inflammation-driven neuronal damage and likely enhancing adaptive plasticity.


Asunto(s)
Esclerosis Múltiple/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Adulto , Citocinas/líquido cefalorraquídeo , Evaluación de la Discapacidad , Femenino , Estudios de Seguimiento , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Examen Neurológico , Estadísticas no Paramétricas , Adulto Joven
4.
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
5.
J Neurovirol ; 23(3): 369-375, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-27995575

RESUMEN

In the USA, increased cerebrospinal fluid (CSF) inflammatory cytokines have been observed in antiretroviral therapy (ART)-naive, HIV-seropositive individuals with HIV-associated neurocognitive disorder (HAND). We characterized the relationship between HAND and CSF biomarker expression in ART-naive, HIV-seropositive individuals in Rakai, Uganda. We analyzed CSF of 78 HIV-seropositive, ART-naive Ugandan adults for 17 cytokines and 20 neurodegenerative biomarkers via Luminex multiplex assay. These adults underwent neurocognitive assessment to determine their degree of HAND. We compared biomarker concentrations between high and low CD4 groups and across HAND classifications, adjusting for multiple comparisons. Individuals with CD4 <200 cells/µL (N = 38) had elevated levels of CSF Interleukin (IL)-2, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF-α, matrix metalloproteinase (MMP)-1, MMP-7, and S100 calcium-binding protein B (S100B) and lower levels of amyloid ß42. Individuals with CD4 351-500 cells/µL (N = 40) had significantly higher CSF levels of interleukin (IL)-1ß, amyloid ß42, and soluble receptor for advanced glycation end products (sRAGE). Increasing levels of S100B, platelet-derived growth factor-AA (PDGF-AA), brain-derived neurotrophic factor (BDNF), and sRAGE were associated with decreased odds of mild neurocognitive disorder (n = 22) or HIV-associated dementia (n = 15) compared with normal function (n = 30) or asymptomatic neurocognitive impairment (n = 11). Increased levels of interferon (IFN)-γ were associated with increased odds of mild neurocognitive impairment or HIV-associated dementia relative to normal or asymptomatic neurocognitive impairment. Proinflammatory CSF cytokines, chemokines, and neurodegenerative biomarkers were present in increasing concentrations with advanced immunosuppression and may play a role in the development of HAND. The presence of select CNS biomarkers may also play a protective role in the development of HAND.


Asunto(s)
Complejo SIDA Demencia/líquido cefalorraquídeo , Complejo SIDA Demencia/diagnóstico , Linfocitos T CD4-Positivos/inmunología , Complejo SIDA Demencia/inmunología , Complejo SIDA Demencia/fisiopatología , Adulto , Péptidos beta-Amiloides/líquido cefalorraquídeo , Péptidos beta-Amiloides/inmunología , Biomarcadores/líquido cefalorraquídeo , Factor Neurotrófico Derivado del Encéfalo/líquido cefalorraquídeo , Factor Neurotrófico Derivado del Encéfalo/inmunología , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/patología , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/líquido cefalorraquídeo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/inmunología , Humanos , Interleucina-12/líquido cefalorraquídeo , Interleucina-12/inmunología , Interleucina-2/líquido cefalorraquídeo , Interleucina-2/inmunología , Masculino , Metaloproteinasa 1 de la Matriz/líquido cefalorraquídeo , Metaloproteinasa 1 de la Matriz/inmunología , Metaloproteinasa 7 de la Matriz/líquido cefalorraquídeo , Metaloproteinasa 7 de la Matriz/inmunología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Fragmentos de Péptidos/líquido cefalorraquídeo , Fragmentos de Péptidos/inmunología , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/inmunología , Estudios Prospectivos , Receptor para Productos Finales de Glicación Avanzada/sangre , Receptor para Productos Finales de Glicación Avanzada/inmunología , Subunidad beta de la Proteína de Unión al Calcio S100/líquido cefalorraquídeo , Subunidad beta de la Proteína de Unión al Calcio S100/inmunología , Factor de Necrosis Tumoral alfa/líquido cefalorraquídeo , Factor de Necrosis Tumoral alfa/inmunología , Uganda
6.
J Neuroimmunol ; 279: 1-6, 2015 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-25669992

RESUMEN

The CXC chemokines (CXC-motif ligand 12 and CXC-motif ligand 14) and platelet-derived growth factor are suggested to modulate remyelination in the course of many demyelinating diseases. The present study compared the difference in the brain levels of these chemokines between patients with idiopathic demyelinating optic neuritis (IDON) and neuromyelitis optica (NMO) by measuring their concentrations in the cerebrospinal fluid using an enzyme linked immunosorbent assay. Our data indicate that the prognosis of neuritis depends on the remyelinating process that is impaired due to decreased chemokines. The much lower levels of chemokines would specifically indicate the severe neuritis, such as NMO.


Asunto(s)
Quimiocina CXCL12/líquido cefalorraquídeo , Quimiocinas CXC/líquido cefalorraquídeo , Mielitis/patología , Neuromielitis Óptica/patología , Neuritis Óptica/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Adulto , Análisis de Varianza , Encéfalo/patología , Ensayo de Inmunoadsorción Enzimática , Potenciales Evocados Visuales/fisiología , Femenino , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Mielitis/líquido cefalorraquídeo , Mielitis/complicaciones , Examen Neurológico , Neuromielitis Óptica/líquido cefalorraquídeo , Neuritis Óptica/complicaciones , Neuritis Óptica/patología , Curva ROC , Índice de Severidad de la Enfermedad , Síndrome
7.
Zhonghua Yan Ke Za Zhi ; 51(12): 901-6, 2015 Dec.
Artículo en Chino | MEDLINE | ID: mdl-26888271

RESUMEN

OBJECTIVE: To explore the predictive value of the prognosis and outcome for optic neuritis (ON) and neuromyelitis optica (NMO) by investigating the levels and variation of CXCL12, PDGF and CXCL14 in CSF of patients with ON and NMO. METHODS: Retrospective study. Thirty-five patients with ON, 10 patients with NMO and 10 patients with cerebral venous sinus thrombosis (CVST) were scheduled in the research unit from September 2012 to September 2013 in Neuro-Ophthalmology Department of PLA General Hospital. Clinical data and cerebrospinal fluid (CSF) parameters were collected. CXCL12, PDGF and CXCL14 concentrations were measured in CSF using enzyme linked immunosorbent assay (ELISA). The CXCL12, PDGF and CXCL14 levels in CSF were compared by using ANOVA in different diseases with different phases and recurrent cases found by MRI. Multiple comparisons were used by LSD method. The comparison of positive rate for MRI in ON different phases was used by exact probability. Meanwhile, correlation analysis was conducted between CXCL12, PDGF, CXCL14 and white blood cells (WBC), IgG and protein in CSF. RESULTS: Compared with NMO group (3.69±0.35, 2.04±0.24, 7.05±0.94), the CXCL12, PDGF and CXCL14 levels in CSF were higher in ON (4.39±0.51, 2.51±0.39, 8.65±1.55) and CVST(4.84± 0.49, 2.79±0.47, 10.53±1.11) group (F=14.593, 10.060, 10.003,P<0.001, <0.001, <0.001), especially the CXCL12, PDGF and CXCL14 levels in CSF of CVST group patients were higher than that in ON group. Among them, the CXCL12 and PDGF levels in CSF were higher in acute phase of ON (4.63±0.50, 2.65±0.40) and CVST(4.84±0.49, 2.79±0.47) group than stationary phase of ON (4.13±0.39, 2.34±0.32) group (F=8.823, 4.906, P=0.001, 0.012). In addition, 28 of 35 ON patients were conducted the cerebral or orbital magnetic resonance imaging (MRI). The result showed that the CXCL12 and PDGF levels in CSF of patients with positive finding in MRI (3.96±0.30, 2.23±0.16) were higher than those patients with negative finding in MRI (4.64±0.42, 2.62±0.42) (t=-4.754, -2.977, all P<0.01). Besides that, there was higher correlation between the CXCL12 level and PDGF in CSF (P<0.01). CONCLUSIONS: Reduced concentration of cytokine that promoted remyelination such as CXCL12 and PDGF in cerebrospinal fluid of the ON and NMO patients may predict a bad myelin regeneration.


Asunto(s)
Quimiocina CXCL12/líquido cefalorraquídeo , Quimiocinas CXC/líquido cefalorraquídeo , Neuromielitis Óptica/líquido cefalorraquídeo , Neuritis Óptica/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Análisis de Varianza , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunoglobulina G/líquido cefalorraquídeo , Recuento de Leucocitos , Vaina de Mielina/fisiología , Neuromielitis Óptica/sangre , Neuritis Óptica/sangre , Pronóstico , Regeneración , Estudios Retrospectivos , Trombosis de los Senos Intracraneales/líquido cefalorraquídeo
8.
Neuromolecular Med ; 16(2): 490-8, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24671722

RESUMEN

During multiple sclerosis (MS) inflammatory attacks, and in subsequent clinical recovery phases, immune cells contribute to neuronal and oligodendroglial cell survival and tissue repair by secreting growth factors. Animal studies showed that growth factors also play a substantial role in regulating synaptic plasticity, and namely in long-term potentiation (LTP). LTP could drive clinical recovery in relapsing patients by restoring the excitability of denervated neurons. We recently reported that maintenance of synaptic plasticity reserve is crucial to contrast clinical deterioration in MS and that the platelet-derived growth factor (PDGF) may play a key role in its regulation. We also reported that a Hebbian form of LTP-like cortical plasticity, explored by paired associative stimulation (PAS), correlates with clinical recovery from a relapse in MS. Here, we explored the role of PDGF in clinical recovery and in adaptive neuroplasticity in relapsing-remitting MS (RR-MS) patients. We found a correlation between the cerebrospinal fluid (CSF) PDGF concentrations and the extent of clinical recovery after a relapse, as full recovery was more likely observed in patients with high PDGF concentrations and poor recovery in subjects with low PDGF levels. Consistently with the idea that PDGF-driven synaptic plasticity contributes to attenuate the clinical consequences of tissue damage in RR-MS, we also found a striking correlation between CSF levels of PDGF and the amplitude of LTP-like cortical plasticity explored by PAS. CSF levels of fibroblast growth factor, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor did not correlate with clinical recovery nor with measures of synaptic transmission and plasticity.


Asunto(s)
Potenciación a Largo Plazo/fisiología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Factor de Crecimiento Derivado de Plaquetas/fisiología , Adulto , Convalecencia , Electromiografía , Potenciales Evocados Motores , Femenino , Factores de Crecimiento de Fibroblastos/líquido cefalorraquídeo , Factor Estimulante de Colonias de Granulocitos/líquido cefalorraquídeo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/líquido cefalorraquídeo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Corteza Motora/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Índice de Severidad de la Enfermedad , Estimulación Magnética Transcraneal , Adulto Joven
9.
J Neurosci ; 33(49): 19112-9, 2013 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-24305808

RESUMEN

Neuroplasticity is essential to prevent clinical worsening despite continuing neuronal loss in several brain diseases, including multiple sclerosis (MS). The precise nature of the adaptation mechanisms taking place in MS brains, ensuring protection from disability appearance and accumulation, is however unknown. Here, we explored the hypothesis that long-term synaptic potentiation (LTP), potentially able to minimize the effects of neuronal loss by providing extra excitation of denervated neurons, is the most relevant form of adaptive plasticity in stable MS patients, and it is disrupted in progressing MS patients. We found that LTP, explored by means of transcranial magnetic theta burst stimulation over the primary motor cortex, was still possible, and even favored, in stable relapsing-remitting (RR-MS) patients, whereas it was absent in individuals with primary progressive MS (PP-MS). We also provided evidence that platelet-derived growth factor (PDGF) plays a substantial role in favoring both LTP and brain reserve in MS patients, as this molecule: (1) was reduced in the CSF of PP-MS patients, (2) enhanced LTP emergence in hippocampal mouse brain slices, (3) was associated with more pronounced LTP in RR-MS patients, and (4) was associated with the clinical compensation of new brain lesion formation in RR-MS. Our results show that brain plasticity reserve, in the form of LTP, is crucial to contrast clinical deterioration in MS. Enhancing PDGF signaling might represent a valuable treatment option to maintain brain reserve and to attenuate the clinical consequences of neuronal damage in the progressive phases of MS and in other neurodegenerative disorders.


Asunto(s)
Esclerosis Múltiple/fisiopatología , Plasticidad Neuronal/fisiología , Factor de Crecimiento Derivado de Plaquetas/fisiología , Transducción de Señal/fisiología , Sinapsis/fisiología , Adulto , Animales , Encéfalo/fisiología , Corteza Cerebral/fisiología , Progresión de la Enfermedad , Estimulación Eléctrica , Fenómenos Electrofisiológicos , Potenciales Evocados/fisiología , Femenino , Humanos , Potenciación a Largo Plazo/fisiología , Imagen por Resonancia Magnética , Masculino , Ratones , Ratones Endogámicos C57BL , Esclerosis Múltiple Crónica Progresiva/líquido cefalorraquídeo , Esclerosis Múltiple Crónica Progresiva/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Ritmo Teta/fisiología , Estimulación Magnética Transcraneal
10.
Eur Neurol ; 68(6): 329-43, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23095669

RESUMEN

Similar to atherosclerosis, platelet-derived growth factor (PDGF)-BB, a major growth factor for vascular smooth muscle cells, is produced in arterial walls to repair arteries after subarachnoid hemorrhage (SAH). On review of a series of research articles that focus on defensive host responses to SAH, PDGF-BB is identified as a spasmogen, based on the following findings: (1) foreign substances injected into the subarachnoid space cause persistent constriction of cerebral arteries with a time course and histological features almost identical to those seen after SAH; (2) persistent constriction induced by SAH or a foreign substance is dependent on the complement system; (3) the complement system, which stimulates platelets, macrophages and endothelial cells to secrete PDGF-BB, is activated in both the cerebrospinal fluid (CSF) and plasma immediately after SAH; (4) PDGF-BB levels in the CSF are significantly elevated in patients with delayed cerebral ischemia; (5) the immunodensity of PDGF-BB in the arterial walls correlates well with the severity of cerebral vasospasm; (6) intracisternal injection of PDGF-BB induces persistent constriction of cerebral arteries in a dose-dependent manner; (7) prolonged contact with blood clots promotes the contractile response of cerebral arteries to PDGF-BB, and (8) administration of an antagonist of PDGF-BB function suppresses the development of cerebral vasospasm.


Asunto(s)
Aterosclerosis/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Hemorragia Subaracnoidea/metabolismo , Vasoespasmo Intracraneal/metabolismo , Animales , Aterosclerosis/fisiopatología , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatología , Humanos , Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/farmacología , Hemorragia Subaracnoidea/fisiopatología , Vasoespasmo Intracraneal/fisiopatología
11.
Eur J Neurol ; 19(2): 241-7, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21771201

RESUMEN

BACKGROUND AND PURPOSE: Fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor-A (PDGF-AA) are potent modulators of oligodendrocytes, the main responsible cells for myelin regeneration. We measured FGF-2 and PDGF-AA in the sera and cerebrospinal fluid (CSF) of patients with relapsing-remitting multiple sclerosis (RR-MS) and compared these values with control subjects. METHODS: Twenty-three patients with RR-MS and 23 subjects without inflammatory and demyelinating diseases were included. Serum samples of the patients were collected in both relapse and remission phases and were analyzed with ELISA method. CSF was drawn during the relapse period. Blood and CSF were drawn from control subjects for comparison. Wilcoxon and Mann-Whitney U-test and Spearman's rank correlation were used for analysis. P values of <0.05 were considered significant. RESULTS: Age and sex distribution were similar in both groups. Serum values of FGF-2 were higher in relapse phase compared with remission phase, with a trend toward significance (P=0.052). CSF PDGF-AA showed significant negative correlation with disease duration (correlation coefficient=-0.58, P=0.004). Serum levels of PDGF did not differ between two phases significantly. There was no difference in serum and CSF values of these factors between patients and controls. When we compared patients with prolonged disease with controls, a significant difference between the CSF levels of PDGF-AA was observed (mean±SEM 2.78±0.8 in controls vs. 0.55±0.29 in patients with MS≥2 years, P<0.05). CONCLUSION: Our study was the first to show that CSF PDGF-AA is related to disease duration. Supporting previous findings we showed that serum and CSF levels of these factors are weak indicators of disease severity.


Asunto(s)
Factor 2 de Crecimiento de Fibroblastos/metabolismo , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Adolescente , Adulto , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Femenino , Factor 2 de Crecimiento de Fibroblastos/sangre , Factor 2 de Crecimiento de Fibroblastos/líquido cefalorraquídeo , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Índice de Severidad de la Enfermedad
13.
Stroke ; 34(2): 427-33, 2003 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-12574555

RESUMEN

BACKGROUND AND PURPOSE: During vasospasm after subarachnoid hemorrhage (SAH), cerebral blood vessels show structural changes consistent with the actions of vascular mitogens. We measured platelet-derived vascular growth factors (PDGFs) in the cerebrospinal fluid (CSF) of patients after SAH and tested the effect of these factors on cerebral arteries in vivo and in vitro. METHODS: CSF was sampled from 14 patients after SAH, 6 patients not suffering SAH, and 8 normal controls. ELISA was performed for PDGF-AB, transforming growth factor-beta1, and vascular endothelial growth factor. A mouse model was used to compare cerebral vascular cell proliferation and PDGF staining in SAH compared with sham-operated controls. Normal human pial arteries were incubated for 7 days in vitro, 2 groups with human blood clot and 1 with and 1 without PDGF antibodies. RESULTS: PDGF-AB concentrations in CSF from SAH patients were significantly higher than those from non-SAH patients and normal controls, both during the first week after SAH and for all time points measured. Smooth muscle and fibroblast proliferation was observed after SAH in the mouse model, and this cellular replication was observed in conjunction with PDGF protein at the sites of thrombus. In human pial arteries, localized thrombus stimulated vessel wall proliferation, and proliferation was blocked by neutralizing antibodies directed against PDGFs. CONCLUSIONS: Vascular mitogens are increased in the CSF of patients after SAH. Proliferation of cells in the vascular wall is associated with perivascular thrombus. Cellular proliferation and subsequent vessel wall thickening may contribute to the syndrome of delayed cerebral vasospasm.


Asunto(s)
Músculo Liso Vascular , Hemorragia Subaracnoidea/complicaciones , Vasoespasmo Intracraneal/etiología , Vasoespasmo Intracraneal/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos/farmacología , División Celular/efectos de los fármacos , Arterias Cerebrales/patología , Arterias Cerebrales/fisiopatología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Factores de Crecimiento Endotelial/líquido cefalorraquídeo , Ensayo de Inmunoadsorción Enzimática , Femenino , Fibroblastos/patología , Humanos , Técnicas In Vitro , Péptidos y Proteínas de Señalización Intercelular/líquido cefalorraquídeo , Linfocinas/líquido cefalorraquídeo , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/patología , Piamadre/irrigación sanguínea , Piamadre/patología , Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Hemorragia Subaracnoidea/patología , Trombosis/patología , Factor de Crecimiento Transformador beta/líquido cefalorraquídeo , Factor de Crecimiento Transformador beta1 , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular , Vasoespasmo Intracraneal/líquido cefalorraquídeo
14.
Acta Neurochir (Wien) ; 143(8): 811-8; discussion 819, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11678402

RESUMEN

BACKGROUND: The aim of this prospective study was to evaluate the significance of growth factors as determinants of the pathological degree of neovascularisation found in the parietal neomembrane of chronic subdural hematoma (CSH). Thus far the pathogenesis of the vascularisation has not been elucidated. METHOD: The concentrations of growth factors, i.e. vascular endothelial derived growth factor (VEGF), basic fibroblast growth factor (bFGF) and platelet derived growth factor (PDGF) were determined using ELISA technique in hematoma fluid and serum of 20 patients with uni- or bilateral CSH. For comparison, growth factor concentrations were determined in cerebrospinal fluid (CSF) of patients undergoing diagnostic myelography. FINDINGS: Concentrations of VEGF and bFGF were significantly (p < 0.001) increased in the hematoma fluid as compared with serum (VEGFh = 8.142 pg/ml, bFGFh = 8.7 pg/ml versus VEGFS = 368 pg/ml, bFGF, = 1.8 pg/ml). In contrast, PDGF concentration was significantly (p < 0.001) lower in the hematoma (PDGFh = 3,456 pg/ml versus PDGF, = 31,937 pg/ml). The serum levels for VEGF, bFGF and PDGF in CSH patients lay within the range of normal volunteers. No growth factors were found in normal CSF. INTERPRETATION: These results reveal a specific distribution pattern of growth factors in CSH patients. This pattern suggests that CSH may be considered a member of the angiogenic disease family.


Asunto(s)
Factores de Crecimiento Endotelial/líquido cefalorraquídeo , Factor 2 de Crecimiento de Fibroblastos/líquido cefalorraquídeo , Hematoma Subdural Crónico/líquido cefalorraquídeo , Linfocinas/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Anciano , Anciano de 80 o más Años , Barrera Hematoencefálica/fisiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Hematoma Subdural Crónico/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Valores de Referencia , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial Vascular
15.
Acta Neurochir (Wien) ; 141(8): 861-5; discussion 865-6, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10536723

RESUMEN

The aim of this study was to evaluate the following questions: Can the platelet-derived growth factor (PDGF-AB) be identified in the serum and cerebro spinal fluid (CSF) of dogs? Is there an increase in the concentration of PDGF-AB following experimental subarachnoid haemorrhage (SAH)? Is the increase in concentration related to the angiographic cerebral vasospasm of the basilar artery. The "double haemorrhage" model was applied in seven dogs to produce experimental SAH with determination of angiographic vasospasm in the basilar artery. Blood and CSF samples were taken on the first, third and eighth days. The analyses were performed with an ELISA human PDGF-AB antibody kit (quantikine human PDGF-AB, R&D Systems, Minneapolis, USA). The average PDGF-AB base value in the serum on the day before the SAH was 410.77 +/- 177.56 pg/ml, in the CSF it was 6.43 +/- 3.19 pg/ml. There was a significant (p = 0.05) increase in the concentration of PDGF-AB (third day 717.35 pg/ml, eighth day 918.07 pg/ml) in the serum of all animals. No significant increase was found in the CSF samples of any animal. In summary, a PDGF-AB like immune reactivity was found in the serum of dogs with the human PDGF-AB ELISA kit and the concentration of PDGF-AB in the serum increased after experimental SAH but not in CSF, but there was no relationship between the increase in PDGF-AB serum concentration and angiographic vasospasm.


Asunto(s)
Arteria Basilar/patología , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Proteínas Recombinantes/sangre , Proteínas Recombinantes/líquido cefalorraquídeo , Hemorragia Subaracnoidea/inmunología , Vasoespasmo Intracraneal/etiología , Vasoespasmo Intracraneal/inmunología , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Perros , Ensayo de Inmunoadsorción Enzimática , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/inmunología , Proteínas Recombinantes/inmunología , Hemorragia Subaracnoidea/sangre , Hemorragia Subaracnoidea/líquido cefalorraquídeo , Hemorragia Subaracnoidea/complicaciones
16.
Clin Neurol Neurosurg ; 99 Suppl 2: S218-20, 1997 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9409441

RESUMEN

We investigated the levels of angiogenic growth factors in cerebrospinal fluid (CSF) from patients with Moyamoya disease and from those with atherosclerotic occlusive disease to evaluate the relationship of these factors to the pathogenesis of Moyamoya disease. CSF from Moyamoya patients contained significantly higher concentrations of basic fibroblast growth factor (b-FGF) (P < 0.05). The b-FGF level was apparently elevated in patients with well developed neovascularization after indirect revascularization surgery (P < 0.01). The other angiogenic factors were not significantly elevated compared with those of the control group.


Asunto(s)
Factor 2 de Crecimiento de Fibroblastos/líquido cefalorraquídeo , Enfermedad de Moyamoya/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Factor de Crecimiento Transformador beta/líquido cefalorraquídeo , Adulto , Arterias Cerebrales/patología , Revascularización Cerebral , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Moyamoya/patología , Enfermedad de Moyamoya/cirugía , Túnica Íntima/patología
17.
Acta Neurochir (Wien) ; 139(4): 319-24, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9202771

RESUMEN

Platelet derived growth factor (PDGF) was identified as a powerful mitogenic growth factor which is released from activated platelets and has a marked activity as vasoconstrictor agent. In the present study we have measured cisternal cerebrospinal fluid (CSF) levels of PDGF in 72 patients operated on for intracranial aneurysm in order to verify whether it might be related to the clinical aspects of SAH with special regard to symptomatic vasospasm. CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern the nearest to the aneurysm before aneurysm isolation and exclusion. The specimen were frozen in liquid nitrogen and stored at -80 degrees C until analysis. PDGF was measured using a commercially available reagent. Values are expressed as pg/ml of CSF. In 18 cases no radiological and clinical signs of SAH were detected and the mean cisternal CSF level of PDGF was 885.0 +/- 104.5 pg/ml; 20 patients were operated on between day 1 and 3 from the last SAH episode: mean cisternal CSF level of PDGF was 1917.5 +/- 459.4 pg/ml. In 34 patients treated with delayed surgery protocol, mean cisternal CSF level of PDGF was 995.3 +/- 73.8 pg/ml. Statistical analysis showed significant differences between groups (P: 0.011). In the subgroup of patients operated on within day 3 after SAH, 6 presented vasospasm and had mean cisternal CSF PDGF level which was significantly higher (P < 0.01) than in 14 patients without vasospasm. In the delayed "surgical" patients there was no significant difference in cisternal CSF levels of PDGF considering the occurrence of vasospasm. The results of the present study suggest that (a) after SAH there is a significant release of PDGF early after SAH and (b) higher levels of PDGF found in cisternal CSF of patients operated on within 72 hours after SAH may be predictive of symptomatic vasospasm.


Asunto(s)
Aneurisma Intracraneal/cirugía , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Hemorragia Subaracnoidea/metabolismo , Adulto , Femenino , Humanos , Aneurisma Intracraneal/metabolismo , Masculino , Hemorragia Subaracnoidea/cirugía
18.
Br J Cancer ; 69(5): 952-6, 1994 May.
Artículo en Inglés | MEDLINE | ID: mdl-8180030

RESUMEN

The aim of this study was to determine the concentration of PDGF in vivo in neoplastic and non-neoplastic brain lesions. Fluid from cystic lesions and cerebrospinal fluid was tested in a radioreceptor assay that detects all described PDGF isoforms. High concentration of PDGF were found in cyst fluids from several astrocytomas, one metastatic melanoma, one metastatic lung adenocarcinoma and one intracerebral abscess. The PDGF concentrations were several times higher than the levels known to be required for maximal PDGF effects on cells in vitro. PDGF could also be detected in some non-neoplastic lesions, especially one intracerebral abscess. The finding of high amounts of PDGF in neoplastic lesions strongly supports the possibility that PDGF can be a mediator of tumour and stromal cell growth and motility in vivo. Comparison of PDGF and beta-thromboglobulin concentrations in the same fluids strongly indicates that the PDGF protein is locally produced rather than a result of platelet activation and derangement of the blood-brain barrier.


Asunto(s)
Astrocitoma/química , Neoplasias Encefálicas/química , Quistes/química , Factor de Crecimiento Derivado de Plaquetas/análisis , beta-Tromboglobulina/análisis , Astrocitoma/líquido cefalorraquídeo , Neoplasias Encefálicas/líquido cefalorraquídeo , Quistes/líquido cefalorraquídeo , Humanos , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , beta-Tromboglobulina/líquido cefalorraquídeo
19.
Brain Res Bull ; 27(3-4): 327-32, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1720341

RESUMEN

In the present study, the relations between acidic and basic fibroblast growth factors (aFGF and bFGF, respectively), platelet-derived growth factor (PDGF), and food intake were studied. When aFGF-, bFGF-, and PDGF-like activity in cerebrospinal fluid (CSF) was examined by bioassay, the activity of those factors significantly increased in postfeeding CSF, compared to prefeeding CSF. Injections of aFGF, bFGF, aFGF (synthetic amino-terminal peptide of aFGF), and PDGF into the third cerebral ventricle decreased food intake, and injections of anti-aFGF, anti-bFGF, and anti-aFGF antibodies into the lateral hypothalamus (LHA) increased food intake. The activity of LHA glucose-sensitive neurons was inhibited by electrophoretic application of aFGF. These results suggest that aFGF, bFGF and PDGF have in vivo physiological roles in the central nervous system, distinct from those as mitogens.


Asunto(s)
Ingestión de Alimentos/efectos de los fármacos , Factor 1 de Crecimiento de Fibroblastos/farmacología , Factor 2 de Crecimiento de Fibroblastos/farmacología , Factor de Crecimiento Derivado de Plaquetas/farmacología , Animales , Anticuerpos/administración & dosificación , Anticuerpos/fisiología , Encéfalo/fisiología , Células Quimiorreceptoras/efectos de los fármacos , Factor 1 de Crecimiento de Fibroblastos/líquido cefalorraquídeo , Factor 1 de Crecimiento de Fibroblastos/inmunología , Factor 2 de Crecimiento de Fibroblastos/líquido cefalorraquídeo , Factor 2 de Crecimiento de Fibroblastos/inmunología , Hipotálamo/fisiología , Inyecciones , Inyecciones Intraventriculares , Masculino , Fragmentos de Péptidos/farmacología , Factor de Crecimiento Derivado de Plaquetas/líquido cefalorraquídeo , Factor de Crecimiento Derivado de Plaquetas/inmunología , Ratas , Ratas Endogámicas
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