Search results for "Sclerosis"
showing 10 items of 1583 documents
Impact of treatment with dimethyl fumarate on sleep quality in patients with relapsing-remitting multiple sclerosis: A multicentre Italian wearable t…
2023
Background Sleep disorders are common in patients with multiple sclerosis and have a bidirectional interplay with fatigue and depression. Objective To evaluate the effect of treatment with oral dimethyl fumarate on the quality of sleep in relapsing-remitting multiple sclerosis. Methods This was a multicentre observational study with 223 relapsing-remitting multiple sclerosis subjects starting treatment with dimethyl fumarate ( n=177) or beta interferon ( n=46). All patients underwent subjective (Pittsburgh Sleep Quality Index) and objective (wearable tracker) measurements of quality of sleep. Fatigue, depression, and quality of life were also investigated and physical activity was monitored…
Monocyte-derived dendritic cells of patients with coronary artery disease show an increased expression of costimulatory molecules CD40, CD80 and CD86…
2007
Background Atherosclerosis is a disease triggered by diverse exogenous stimuli and sustained by chronic inflammatory processes. Dendritic cells (DCs) are key regulatory antigen-presenting cells and play a crucial role in regulating the adaptive and innate immune system in any chronic inflammatory process. DCs are present in atherosclerotic lesions in the areas of the highest T-cell density. So far, their role in atherosclerosis has not been fully elucidated. We investigated the phenotypic properties of DCs in patients with coronary artery disease (CAD) in comparison to healthy individuals. Methods Peripheral blood monocytes were isolated from 50 patients with CAD and 19 healthy individuals …
Control of spasticity in a multiple sclerosis model using central nervous system-excluded CB1 cannabinoid receptor agonists
2014
The purpose of this study was the generation of central nervous system (CNS)-excluded cannabinoid receptor agonists to test the hypothesis that inhibition of spasticity, due to CNS autoimmunity, could be controlled by affecting neurotransmission within the periphery. Procedures included identification of chemicals and modeling to predict the mode of exclusion; induction and control of spasticity in the ABH mouse model of multiple sclerosis; conditional deletion of CB1 receptor in peripheral nerves; side-effect profiling to demonstrate the mechanism of CNS-exclusion via drug pumps; genome-wide association study in N2(129×ABH) backcross to map polymorphic cannabinoid drug pump; and sequencing…
Role of Sortilin in Models of Autoimmune Neuroinflammation
2015
Abstract The proneurotrophin receptor sortilin is a protein with dual functions, being involved in intracellular protein transport, as well as cellular signal transduction. The relevance of the receptor for various neuronal disorders, such as dementia, seizures, and brain injury, is well established. In contrast, little is known about the role of sortilin in immune cells and inflammatory diseases. The aim of our study was to elucidate the distribution of sortilin in different immune cell types in mice and humans and to analyze its function in autoimmune CNS inflammation. Sortilin was expressed most profoundly in murine and human macrophages and dendritic cells and to a much lesser extent in…
Cytosolic RIG-I–like helicases act as negative regulators of sterile inflammation in the CNS
2011
The action of cytosolic RIG-I-like helicases (RLHs) in the CNS during autoimmunity is largely unknown. Using a mouse model of multiple sclerosis, we found that mice lacking the RLH adaptor IPS-1 developed exacerbated disease that was accompanied by markedly higher inflammation, increased axonal damage and elevated demyelination with increased encephalitogenic immune responses. Furthermore, activation of RLH ligands such as 5'-triphosphate RNA oligonucleotides decreased CNS inflammation and improved clinical signs of disease. RLH stimulation repressed the maintenance and expansion of committed T(H)1 and T(H)17 cells, whereas T-cell differentiation was not altered. Notably, T(H)1 and T(H)17 s…
Immune regulatory neural stem/precursor cells protect from central nervous system autoimmunity by restraining dendritic cell function.
2009
Background: The systemic injection of neural stem/precursor cells (NPCs) provides remarkable amelioration of the clinicopathological features of experimental autoimmune encephalomyelitis (EAE). This is dependent on the capacity of transplanted NPCs to engage concurrent mechanisms of action within specific microenvironments in vivo. Among a wide range of therapeutic actions alternative to cell replacement, neuroprotective and immune modulatory capacities of transplanted NPCs have been described. However, lacking is a detailed understanding of the mechanisms by which NPCs exert their therapeutic plasticity. This study was designed to identify the first candidate that exemplifies and sustains …
OTUB1 inhibits CNS autoimmunity by preventing IFN-γ-induced hyperactivation of astrocytes.
2019
Astrocytes are critical regulators of neuroinflammation in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Growing evidence indicates that ubiquitination of signaling molecules is an important cell‐intrinsic mechanism governing astrocyte function during MS and EAE. Here, we identified an upregulation of the deubiquitinase OTU domain, ubiquitin aldehyde binding 1 (OTUB1) in astrocytes during MS and EAE. Mice with astrocyte‐specific OTUB1 ablation developed more severe EAE due to increased leukocyte accumulation, proinflammatory gene transcription, and demyelination in the spinal cord as compared to control mice. OTUB1‐deficient astrocytes were hy…
Elevated cerebrospinal fluid and plasma homocysteine levels in ALS
2009
BACKGROUND: High cerebrospinal fluid (CSF) and plasma levels of homocysteine (HC) have been reported in certain neurodegenerative disorders, such as Alzheimer's, Parkinson's diseases and, recently, amyotrophic lateral sclerosis (ALS). OBJECTIVES: To assay the CSF and plasma levels of HC in ALS patients and controls, and to evaluate the relationship between HC levels and clinical variables of the disease. METHODS: Cerebrospinal fluid from sixty-nine (M/F 1.87) and plasma from sixty-five ALS patients (M/F 1.83) were taken and stored at -80 degrees C until use. Controls (CSF = 55; plasma = 67) were patients admitted to our hospital for neurological disorders with no known relationship to HC ch…
The Relationship between Gray Matter Quantitative MRI and Disability in Secondary Progressive Multiple Sclerosis
2016
Purpose: In secondary progressive Multiple Sclerosis (SPMS), global neurodegeneration as a driver of disability gains importance in comparison to focal inflammatory processes. However, clinical MRI does not visualize changes of tissue composition outside MS lesions. This quantitative MRI (qMRI) study investigated cortical and deep gray matter (GM) proton density (PD) values and T1 relaxation times to explore their potential to assess neuronal damage and its relationship to clinical disability in SPMS. Materials and Methods: 11 SPMS patients underwent quantitative T1 and PD mapping. Parameter values across the cerebral cortex and deep GM structures were compared with 11 healthy controls, and…
Molecular mechanisms linking neuroinflammation and neurodegeneration in MS.
2013
Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder of the central nervous system (CNS) and one of the leading causes of neurological deficits and disability in young adults in western countries. Current medical treatment mainly influences disease progression via immunomodulatory or immunosuppressive actions. Indeed, MS research has been foremost focused on inflammation in the CNS, but more recent evidence suggests that chronic disability in MS is caused by neurodegeneration. Imaging studies show an early involvement of neurodegeneration as brain atrophy and gray matter lesions can be observed at disease onset. Thus, neuroprotective treatment strategies and the eluc…