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[Mechanisms of Neurodegeneration in Multiple Sclerosis].

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, which results in the formation of primary demyelinating lesions in the white and gray matter, as well as diffuse axonal and neuronal damage. Although there has been substantial progress in drug research in relapsing-remitting MS, treatment of progressive forms of the disease, can be challenging. Diffuse and compartmentalized lymphocyte and macrophage infiltration of the CNS tissue inhibits the differentiation of myelinating mature oligodendrocytes, disrupting the process of remyelination. Chronic inflammat…

Linomide in relapsing and secondary progressive MS: part I: trial design and clinical results. North American Linomide Investigators.

OBJECTIVE: To determine whether linomide (roquinimex) is better than placebo in slowing the time to confirmed clinical worsening in patients with relapsing-remitting (RR) and secondary progressive (SP) MS. METHODS: In this 27-center, randomized, double-blind, placebo-controlled, multiple-dose, phase III trial, 715 patients with active RRMS (n = 90) or SPMS (n = 625) were randomized to receive either linomide (1.0, 2.5, or 7.5 mg orally daily) or placebo. Patients were evaluated at 3-month intervals clinically and with MRI. The planned primary outcome was the time to the development of "confir

The role of glycogen synthase kinase 3 beta in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that leads to progressive neurological disability due to axonal deterioration. Although MS presents profound heterogeneity in the clinical course, its underlying central mechanism is active demyelination and neurodegeneration associated with inflammation. Multiple autoimmune and neuroinflammatory pathways are involved in the demyelination process of MS. Analysis of MS lesions has shown that inflammatory genes are upregulated. Glycogen synthase kinase-3 (GSK-3) is part of the mitogen-activated protein kinase (M…

Axonal loss and neurofilament phosphorylation changes accompany lesion development and clinical progression in multiple sclerosis.

Neuroaxonal damage and loss are increasingly recognized as disability determining features in multiple sclerosis (MS) pathology. However, little is known about the long-term sequelae of inflammatory demyelination on neurons and axons. Spinal cord tissue of 31 MS patients was compared to three amyotrophic lateral sclerosis (ALS) and 10 control subjects. MS lesions were staged according to the density of KiM-1P positive macrophages and microglia and the presence of myelin basic protein (MBP) positive phagocytes. T cells were quantified in the parenchyma and meninges. Neuroaxonal changes were stu…

The relation between inflammation and neurodegeneration in multiple sclerosis brains.

Some recent studies suggest that in progressive multiple sclerosis, neurodegeneration may occur independently from inflammation. The aim of our study was to analyse the interdependence of inflammation, neurodegeneration and disease progression in various multiple sclerosis stages in relation to lesional activity and clinical course, with a particular focus on progressive multiple sclerosis. The study is based on detailed quantification of different inflammatory cells in relation to axonal injury in 67 multiple sclerosis autopsies from different disease stages and 28 controls without neurologic…

Genetic variation associated with the occurrence and progression of neurological disorders.

This paper presents an overview of genetic variation associated with the onset and progression of 14 neurological disorders, focusing primar … within condition. The volume of evidence is greatest for Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis. As for common complex chronic diseases, genome wide association studies have found that validated genomic regions account for a low proportion of heritability. Apart from multiple sclerosis, which shares several su …

Functional cycling ergometry with or without electrical stimulation in individuals with secondary progressive multiple sclerosis: A randomized controlled trial.

BACKGROUND: People with secondary progressive multiple sclerosis (PwSPMS) experience symptoms impacting their ability to walk or exercise. Functional electrical stimulation (FES) cycling is a promising, safe therapeutic intervention for MS, but relatively little is known about its use in PwSPMS with moderate to severe disability. OBJECTIVE: To determine effects of active FES and passive cycling on walking speed and other disability measures in PwSPMS. METHODS: PwSPMS and Expanded Disability Status Scale (EDSS) 5.0-7.0 were randomized to a 12-week FES-assisted or passive (control) cycling int…

Соблюдение и соблюдение требований, предъявляемых к тренировке по прогрессивному многоразовому склерозу: показатели и корреляции в ходе судебного разбирательства по делу CogEx.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Существует ограниченное понимание того, что люди, страдающие прогрессивным множественным склерозом (ПМС), должны соблюдать требования и соблюдать требования, предъявляемые к тренировкам. ЦЕЛИ: В рамках этого вторичного исследовательского анализа данных были проанализированы показатели соблюдения и соблюдения требований в отношении непрерывного обучения с умеренной интенсивностью и обучения с высокой интенсивностью (HIIT) и возможных корреляций между людьми с ПМС в ходе испытания CogEx. МЕТОДЫ: " КогЭкс " - это многообъектное, многоствольное, произвольное, двойн

Совпадение в аннотации оригинала
BACKGROUND: There is limited understanding of adherence and compliance rates for exercise training(ET) in people with progressive multiple sclerosis(PMS). OBJECTIVES: This secondary, exploratory data analysis examined rates of adherence and compliance for continuous, moderate intensity training and high-intensity interval training(HIIT) and possible correla…

Tetracyclines Diminish In Vitro IFN-γ and IL-17-Producing Adaptive and Innate Immune Cells in Multiple Sclerosis.

INTRODUCTION: Limited data from clinical trials in multiple sclerosis (MS) reported that minocycline, a widely used antibiotic belonging to the family of tetracyclines (TCs), exerts a beneficial short-lived clinical effect A similar anti-inflammatory effect of minocycline attributed to a deviation from Th1 to Th2 immune response has been reported in experimental models of MS. Whether such an immunomodulatory mechanism is operated in the human disease remains largely unknown. AIM: To assess the in vitro immunomodulatory effect of tetracyclines, and in particular minocycline and doxycycline, in…

Vaccinations and steroids in MS: effects on disease progression and mood.

OBJECTIVE: To investigate the effects of vaccinations and steroids on disease progression and mood in patients with multiple sclerosis (MS). MATERIAL AND METHODS: Twenty-three patients with clinically definite MS were questioned with respect to vaccination history and the cumulative dose of steroids given during their life-time. EDSS scores and MRI scans of the brain were obtained and used to quantify clinical and MRI disease progression. Mood was assessed by using a self-estimated adjective mood scale. RESULTS: The number of vaccinations showed no effect on disease progression or mood. High…

Therapeutic potential of luteolin in neurodegenerative disorders: targeting Nrf2, NFĸB, MAPK, and JAK-STAT pathways to combat neuroinflammation and apoptosis.

Neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's disease, Multiple sclerosis and Amyotrophic Lateral Sclerosis, are characterized by progressive neuronal loss, oxidative stress, chronic neuroinflammation, mitochondrial dysfunction, and apoptosis. The Nrf2/ARE, IĸB/NFĸB, MAPK/AP-1, and JAK-STAT signaling pathways play a pivotal role in these pathological processes, making them promising therapeutic targets. Luteolin, a naturally occurring flavonoid, has demonstrated potent antioxidant, anti-inflammatory, and neuroprotective properties by modulating these interconnect…

Immunophenotypic characterization of CSF B cells in virus-associated neuroinflammatory diseases.

Intrathecal antibody synthesis is a well-documented phenomenon in infectious neurological diseases as well as in demyelinating diseases, but little is known about the role of B cells in the central nervous systems. We examined B cell and T cell immunophenotypes in CSF of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) compared to healthy normal donors and subjects with the other chronic virus infection and/or neuroinflammatory diseases including HIV infection, multiple sclerosis (MS) and progressive multifocal leukoencephalopathy. Antibody secreting B cells (A…

The role of the Epstein-Barr virus receptor CD21 in multiple sclerosis.

Multiple Sclerosis (MS) is characterised by a chronic inflammation and demyelination of brain and spinal cord with a yet unknown aetiology. Based on multiple epidemiological and immunological studies, which suggest a role of Epstein-Barr virus (EBV) infection in the pathogenesis of MS, we investigated CD21 (CR2, complement receptor type 2), which serves as the EBV receptor. Serum concentrations of soluble CD21 receptor (sCD21) were determined in MS patients and controls. In accordance with findings in other autoimmune disorders decreased sCD21 levels were found in MS patients. On ß-IFN treatme…

A monoclonal natural human IgM protects axons in the absence of remyelination.

BACKGROUND: Whereas demyelination underlies early neurological symptoms in multiple sclerosis (MS), axonal damage is considered critical for permanent chronic deficits. Intracerebral infection of susceptible mouse strains with Theiler's murine encephalomyelitis virus (TMEV) results in chronic induced demyelinating disease (TMEV-IDD) with progressive axonal loss and neurologic dysfunction similar to progressive forms of MS. We previously reported that treatment of chronic TMEV-IDD mice with a neurite outgrowth-promoting natural human antibody, HIgM12, improved brainstem NAA concentrations and p…

Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases.

Neurodegeneration is a chronic progressive loss of neuronal cells leading to deterioration of central nervous system (CNS) functionality. It … (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and multiple sclerosis (MS). We also discuss MMP inhibition as a possible therapeutic strategy to treat neurodegenerative diseases.

The Role of PPAR Gamma in Systemic Sclerosis.

Fibrosis is recognized as an important feature of many chronic diseases, such as systemic sclerosis (SSc), an autoimmune disease of unknown etiology, characterized by immune dysregulation and vascular injury, followed by progressive fibrosis affecting the skin and multiple internal organs. SSc has a poor prognosis because no therapy has been shown to reverse or arrest the progression of fibrosis, representing a major unmet medical need. Recently, antifibrotic effects of PPARγ ligands have been studied in vitro and in vivo and some theories have emerged leading to new insights. Aberrant PPARγ f

Nogo-A Antibodies for Progressive Multiple Sclerosis.

Most of the current therapies, as well as many of the clinical trials, for multiple sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate potential therapies for the chronic progressive disease stage of MS. The latter is responsible for the steadily increasing disability in many patients, and there is an urgent need for novel therapies that protect nervous system tissue and enhance axonal growth and/or remyelination. As outlined in this review, solid pre-clinical data suggest neutralization of the neurite outgrowth inhibitor Nogo-A as…

Early structural hub disruption leads to premature functional adaption in multiple sclerosis.

In Multiple Sclerosis, inflammation and neurodegeneration disrupt structural and functional brain networks. While the association between structural connectivity and disability is rather clear, functional connectivity changes are not yet characterised as a physiological response to the disease, as functionally meaningful adaptation or as a deceptive response. We explored the topology of brain networks of 65 Multiple Sclerosis patients over up to seven years in comparison to 59 controls. Connectomes based on probabilistic tractography from diffusion weighted imaging and resting-state MRI, were …

Заболевание дымом при педиатрическом склерозе.

Заболевание дымом при множественном склерозе (MS) относится к хроническим процессам центральной нервной системы, которые происходят после острого воспаления, приводящего к длительной инвалидности. Несмотря на то, что нынешняя терапия эффективно сокращает частоту рецидивов и поражения МРТ, многие люди находятся в процессе развития независимо от активности рецидивов. Хотя клиническая прогрессия необычная в детстве или подростковом возрасте, все больше фактов указывает на то, что субклиническое прогрессивное заболевание биология уже действует даже в этой молодой возрастной группе, что требует ран

Совпадение в аннотации оригинала
Smouldering disease in multiple sclerosis (MS) refers to chronic central nervous system processes that occur beyond acute inflammation, driving long-term disability. Although current therapies effectively reduce relapse rates and MRI lesions, many individuals experience progression independent of relapse activity. While clinical progression is uncommon durin…