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CNS Lesions (cns + lesion)
Selected AbstractsPredictive factors for organic central precocious puberty and utility of simplified gonadotropin-releasing hormone testsPEDIATRICS INTERNATIONAL, Issue 6 2007JIN-HO CHOI Abstract Background: The aim of the present study was to determine whether the clinical presentation of patients with central precocious puberty (CPP) permits differentiation between idiopathic and organic forms, and to examine whether luteinizing hormone (LH) determination in single blood sample after gonadotropin-releasing hormone (GnRH) administration is sufficient to diagnose CPP. Methods: Potential clinical and laboratory predictors for the presence of central nervous system (CNS) abnormalities were assessed. Sensitivities and specificities of LH and follicle-stimulating hormone (FSH) levels at 0, 15, 30, 60, 90 and 120 min were compared after GnRH stimulation. Results: In 45 girls with signs of breast development, 26 were diagnosed as having CPP. The age of onset in patients with organic CPP was 4.75 ± 2.01 years (range 1.2,7.1 years, median 5.0 years), whereas the age in patients with idiopathic CPP was 7.09 ± 0.87 years (range 5.0,7.9 years, median 7.0 years). This parameter is the only one showing statistical significance. In addition, the specimen at 30 min after GnRH stimulation yielded highest sensitivity for the diagnosis of CPP. Conclusions: The earlier the onset of disease, the higher the possibility of presence of CNS lesion. According to the mean GnRH-stimulated LH levels and sensitivity at each time, a single blood sample obtained for LH determined after GnRH administration at 30 min can be used to diagnose CPP. [source] New concepts in bilirubin encephalopathyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2003J. D. Ostrow Abstract Revised concepts of bilirubin encephalopathy have been revealed by studies of bilirubin toxicity in cultured CNS cells and in congenitally jaundiced Gunn rats. Bilirubin neurotoxicity is related to the unbound (free) fraction of unconjugated bilirubin (Bf), of which the dominant species at physiological pH is the protonated diacid, which can passively diffuse across cell membranes. As the binding affinity of plasma albumin for bilirubin decreases strikingly as albumin concentration increases, previously reported Bf values were underestimated. Newer diagnostic tests can detect reversible neurotoxicity before permanent damage occurs from precipitation of bilirubin (kernicterus). Early toxicity can occur at Bf only modestly above aqueous saturation and affects astrocytes and neurons, causing mitochondrial damage, resulting in impaired energy metabolism and apoptosis, plus cell-membrane perturbation, which causes enzyme leakage and hampers transport of neurotransmitters. The concentrations of unbound bilirubin in the cerebro-spinal fluid and CNS cells are probably limited mainly by active export of bilirubin back into plasma, mediated by ABC transporters present in the brain capillary endothelium and choroid plexus epithelium. Intracellular bilirubin levels may be diminished also by oxidation, conjugation and binding to cytosolic proteins. These new concepts may explain the varied susceptibility of neonates to develop encephalopathy at any given plasma bilirubin level and the selective distribution of CNS lesions in bilirubin encephalopathy. They also can suggest better strategies for predicting, preventing and treating this syndrome. [source] Astrocytic factors protect neuronal integrity and reduce microglial activation in an in vitro model of N -methyl- d -aspartate-induced excitotoxic injury in organotypic hippocampal slice culturesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2001Nils P. Hailer Abstract Acute CNS lesions lead to neuronal injury and a parallel glial activation that is accompanied by the release of neurotoxic substances. The extent of the original neuronal damage can therefore be potentiated in a process called secondary damage. As astrocytes are known to secrete immunomodulatory and neuroprotective substances, we investigated whether astrocytic factors can attenuate the amount of neuronal injury as well as the degree of microglial activation in a model of excitotoxic neurodegeneration. Treatment of organotypic hippocampal slice cultures with N-methyl- d -aspartate (NMDA) resulted in a reproducible loss of viable granule cells, partial destruction of the regular hippocampal cytoarchitecture and a concomitant accumulation of amoeboid microglial cells at sites of neuronal damage. Astrocyte-conditioned media reduced the amount of NMDA-induced neuronal injury by 45.3%, diminished the degree of microglial activation and resulted in an improved preservation of the hippocampal cytoarchitecture. Transforming growth factor (TGF)-, failed to act as a neuroprotectant and even enhanced the amount of neuronal injury by 52.5%. Direct effects of astrocytic factors on isolated microglial cells consisted of increased microglial ramification and down-regulated expression of intercellular adhesion molecule-1, whereas incubation with TGF-, had no such effects. In summary, our findings show that hitherto unidentified astrocyte-derived factors that are probably not identical with TGF-, can substantially enhance neuronal survival, either by eliciting direct neuroprotective effects or by modulating the microglial response to neuronal injury. [source] Involvement of gp130-associated cytokine signaling in Müller cell activation following optic nerve lesionGLIA, Issue 7 2010Matthias Kirsch Abstract Ciliary neurotrophic factor (CNTF) and the related cytokine leukemia inhibitory factor (LIF) have been implicated in regulating astrogliosis following CNS lesions. Application of the factors activates astrocytes in vivo and in vitro, and their expression as well as their receptors is upregulated after brain injury. Here, we investigated their function by studying Müller cell activation induced by optic nerve crush in CNTF- and LIF-deficient mice, and in animals with deficiencies in cytokine signaling pathways. In the retina of CNTF,/, mice, basal GFAP expression was reduced, but unexpectedly, injury-induced upregulation in activated Müller cells was increased during the first 3 days after lesion as compared to wild-type animals and this corresponded with higher phosphorylation level of STAT3, an indicator of cytokine signaling. The observation that LIF expression was strongly upregulated in CNTF,/, mice but not in wild-type animals following optic nerve lesion provided a possible explanation. In fact, additional ablation of the LIF gene in CNTF/LIF double knockout mice almost completely abolished early lesion-induced GFAP upregulation in Müller cells and STAT3 phosphorylation. Early Müller cell activation was also eliminated in LIF,/, mice, despite normal CNTF levels, as well as in mutants deficient in gp130/JAK/STAT signaling and in conditional STAT3 knockout mice. Our results demonstrate that LIF signaling via the gp130/JAK/STAT3 pathway is required for the initiation of the astrogliosis-like reaction of retinal Müller cells after optic nerve injury. A potential role of CNTF was possibly masked by a compensatory increase in LIF signaling in the absence of CNTF. © 2010 Wiley-Liss, Inc. [source] Characterization of CD8-positive macrophages infiltrating the central nervous system of rats with chronic autoimmune encephalomyelitisJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2009Keiko Hiraki Abstract CD8+ macrophages appear in the central nervous system (CNS) under various pathological conditions such as trauma and ischemia. Furthermore, macrophages expressing CD8 were found in CNS lesions of chronic, but not acute, experimental autoimmune encephalomyelitis (EAE). To further characterize cells with this phenotype, we examined CD8+ macrophages/monocytes in the CNS and peripheral organs during the course of acute and chronic EAE that had been induced by immunization of rats with myelin basic protein and myelin oligodendrocyte glycoprotein, respectively. Counting CD8+ macrophages in CNS lesions revealed that their numbers increased reaching about 60% of total infiltrating macrophages in chronic EAE, while CD8+ macrophages remained less than 5% throughout the course of acute EAE. Unexpectedly, however, higher abundance of CD8+ monocytes/macrophages in the peripheral blood was found in both acute and chronic EAE. Real-time polymerase chain reaction analysis revealed no significant difference in the levels of chemokines and chemokine receptors of blood CD8+ monocytes between acute and chronic EAE. mRNA expression of perforin, a cytotoxic substance, was up-regulated in CD8+ monocytes compared with that of CD8, monocytes in both acute and chronic EAE. These findings suggest that activated CD8+ macrophages may play a cytotoxic role in chronic EAE lesions and that cells other than CD8+ monocytes/macrophages determined the difference in CNS pathology between acute and chronic EAE. Analysis of CD8+ monocytes/macrophages may provide useful information to permit further dissect the pathomechanisms of multiple sclerosis and to develop effective immunotherapies against autoimmune diseases in the CNS. © 2008 Wiley-Liss, Inc. [source] 18F-fluorodeoxyglucose,positron emission tomography scanning is more useful in followup than in the initial assessment of patients with Erdheim-Chester diseaseARTHRITIS & RHEUMATISM, Issue 10 2009Laurent Arnaud Objective Erdheim-Chester disease (ECD) is a rare form of non,Langerhans' cell histiocytosis. The aim of this study was to assess the value of whole-body scanning with 18F-fluorodeoxyglucose,positron emission tomography (FDG-PET) in a large cohort of ECD patients from a single center. Methods We retrospectively reviewed all PET scans performed on 31 patients with ECD who were referred to our department between 2005 and 2008. PET images were reviewed by 2 independent nuclear medicine specialist physicians and were compared with other imaging modalities performed within 15 days of each PET scan. Results Thirty-one patients (10 women and 21 men; median age 59.5 years) underwent a total of 65 PET scans. Twenty-three patients (74%) were untreated at the time of the initial PET scan, whereas 30 of the 34 followup PET scans (88%) were performed in patients who were undergoing immunomodulatory therapy. Comparison of the initial and followup PET scans with other imaging modalities revealed that the sensitivity of PET scanning varied greatly among the different organs studied (range 4.3,100%), while the specificity remained high (range 69.2,100%). Followup PET scans were particularly helpful in assessing central nervous system (CNS) involvement, since the PET scan was able to detect an early therapeutic response of CNS lesions, even before magnetic resonance imaging showed a decrease in their size. PET scanning was also very helpful in evaluating the cardiovascular system, which is a major prognostic factor in ECD, by assessing the heart and the entire vascular tree during a single session. Conclusion The results of our large, single-center, retrospective study suggest that the findings of a FDG-PET scan may be interesting in the initial assessment of patients with ECD, but its greater contribution is in followup of these patients. [source] | |||||||||||||