Результаты поиска

Target inhibition of SPAK in choroid plexus attenuates T cell infiltration and demyelination in experimental autoimmune encephalomyelitis.

BACKGROUND: Disease-modifying therapies (DMTs) that prevent immune cell infiltration into the brain have demonstrated efficacy in multiple s … we explored the role of Ste20-related proline/alanine-rich kinase (SPAK) in experimental autoimmune encephalomyelitis (EAE). METHODS: We examined the expression patterns of SPAK signaling in ChP using immunofluorescence in the EAE model. To investigate the roles of SPAK, matrix metalloproteinase (MMP) 2 and MMP9 in EAE pathology, we performed ChP-specific gene man …

Oligodendrocyte Precursor Cell-Specific HMGB1 Knockout Reduces Immune Cell Infiltration and Demyelination in Experimental Autoimmune Encephalomyelitis Models.

Infiltration and activation of peripheral immune cells are critical in the progression of multiple sclerosis and its experimental animal model, experimental autoimmune encephalomyelitis (EAE). This study investigates the role of high mobility group box 1 (HMGB1) in oligodendrocyte precursor cells (OPCs) in modulating pathogenic T cells infiltrating the central nervous system through the blood-brain barrier (BBB) by using OPC-specific HMGB1 knockout (KO) mice. We found that HMGB1 released from OPCs promotes BBB disruption, subsequently allowing increased immune cell infiltration. The migration …

CXCL13 Повреждает позвоночник крови, поощряя RNF6/Sqstm1-Ubictiination.

Повреждение позвоночника крови (BSCB) приводит к нарушению иммунной микроокружающей среды в центральной нервной системе во время развития множественного склероза (MS) и экспериментального аллергического энцефаломиэлита (EAE). Тем не менее основные механизмы, связанные с повреждением барьера, по-прежнему недостаточно изучены. Здесь, анализируя белковые профили в периферической сыворотке крови, хемокин (C-X-C motif) Ligand 13 (CXCL13) был определен как возрастающий по мере развития MS и EAE. Отсутствие CXCL13 привело к снижению симптомов EAE, о чем свидетельствует сокращение числа клинических оц

Совпадение в аннотации оригинала
The damage of blood spinal cord barrier (BSCB) is contributing to the disruption of immune microenvironment within central nervous system during the progression of multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). Nevertheless, the underlying mechanisms responsible for barrier impairment remain inadequately understood. Here, by analy…

The role of S-nitrosoglutathione reductase (GSNOR) in T cell-mediated immunopathology of experimental autoimmune encephalomyelitis (EAE).

Previously, we reported that both S-nitrosoglutathione (GSNO), a carrier of cellular nitric oxide, and N6022, an injectable form of GSNO reductase (GSNOR) inhibitor that increases endogenous GSNO levels, alleviate experimental autoimmune encephalomyelitis (EAE) in mice by suppressing Th1 and Th17 immune responses. Building on these findings, we explored the role of GSNOR in EAE pathogenesis and evaluated the efficacy of an orally active GSNOR inhibitor (N91115) in treating the EAE disease. EAE mice exhibited heightened expression/activity of GSNOR in the spinal cord, and the knockout of the GS…

Ovalbumin-specific CD4+ and CD8+ T cells contribute to different susceptibility for Theiler's murine encephalomyelitis virus persistence.

Theiler's murine encephalomyelitis virus (TMEV) is the causative agent of TMEV-induced demyelinating disease (TMEV-IDD); a well-established animal model for the chronic progressive form of human multiple sclerosis (MS). In susceptible mice with an inadequate immune response, TMEV-IDD is triggered by virus persistence and maintained by a T cell mediated immunopathology. OT-mice are bred on a TMEV-resistant C57BL/6 background and own predominantly chicken ovalbumin (OVA)-specific populations of CD8+ T cells (OT-I) or CD4+ T cells (OT-II), respectively. It is hypothesized that the lack of antigen…

KLHL11 antibody-associated autoimmune encephalomyelitis in a middle-aged female patient: a case report and literature review.

HEADINGS: Kelch-like protein 11antibody is a recently identified biomarker for paraneoplastic neurological syndromes associated with germ-ce … positive oligoclonal bands in her CSF. She was diagnosed with KLHL11 antibody-associated autoimmune encephalomyelitis and received high-dose intravenous methylprednisolone pulse therapy. RESULT AND CONCLUSIONS: Clinical outcomes suggest that patients with Kelch-like protein 11 antibody mostly have poor prognoses, excepting our case. We propose that early and appro …

Causal Effects between Gut Microbiome and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Two-Sample Mendelian Randomization Study.

BACKGROUND: Evidence from previous studies have implicated an important association between gut microbiota (GM) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), but whether there is a definite causal relationship between GM and ME/CFS has not been elucidated. METHOD: This study obtained instrumental variables of 211 GM taxa from the Genome Wide Association Study (GWAS), and mendelian randomization (MR) study was carried out to assess the effect of gut microbiota on ME/CFS risk from UK Biobank GWAS (2076 ME/CFS cases and 460,857 controls). Inverse variance weighted (IVW) was th…

Posttreatment Lyme disease syndrome and myalgic encephalomyelitis/chronic fatigue syndrome: A systematic review and comparison of pathogenesis.

Lyme disease is the most common vector-borne illness in the United States and has been causing significant morbidity since its discovery in 1977. It is well-documented that about 10% of patients properly treated with antibiotics never fully recover, but instead go on to develop a chronic illness dubbed, posttreatment Lyme disease syndrome (PTLDS) characterized by severe fatigue, cognitive slowing, chronic pain, and sleep difficulties. This review includes 18 studies that detail the symptoms of patients with PTLDS and uses qualitative analysis to compare them to myalgic encephalitis/chronic fat

Autophagic Molecular Alterations in the Mouse Cerebellum Experimental Autoimmune Encephalomyelitis Model Following Treatment with Cannabidiol and Fluoxetine.

The crosstalk between autophagy and apoptosis is one of the most important processes involved in the cell program death, and several mechani … n in the cerebellum, an important site for white matter in a mouse model of experimental autoimmune encephalomyelitis (EAE). EAE was induced in twenty four adult female C57Bl/6 mice were inducted the EAE model; FLX treatment which was performed (10 mg/kg/IP) and CBD; were treated (5 mg/kg/IP); and their cerebellum was used for Western blotting, real-time PCR to aut …

Efficacy of Vafidemstat in Experimental Autoimmune Encephalomyelitis Highlights the KDM1A/RCOR1/HDAC Epigenetic Axis in Multiple Sclerosis.

Lysine specific demethylase 1 (LSD1; also known as KDM1A), is an epigenetic modulator that modifies the histone methylation status. KDM1A fo … s to be explored. Here, we investigated the effect of ORY-2001 on immune-mediated and virus-induced encephalomyelitis, two experimental models of multiple sclerosis and neuronal damage. Oral administration of ORY-2001 ameliorated clinical signs, reduced lymphocyte egress and infiltration of immune cells into the spinal cord, and prevented demyelination. Interesting …

The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease with an unknown origin. Previous studies showed the involvement of the hypothalamic-pituitary-adrenal (HPA) axis to susceptibility to autoimmune diseases, including MS, and its best-characterized animal model, experimental autoimmune encephalomyelitis (EAE). During MS/EAE, innate immune cells are activated and release cytokines and other inflammatory mediators, leading to a vicious cycle of inflammation. In response to inflammation, the activated HPA axis modulates immune responses via glucocorticoid activity. Because the mechan…

Central Nervous System-Endogenous TLR7 and TLR9 Induce Different Immune Responses and Effects on Experimental Autoimmune Encephalomyelitis.

Innate receptors, including Toll like receptors (TLRs), are implicated in pathogenesis of CNS inflammatory diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). TLR response to pathogens or endogenous signals includes production of immunoregulatory mediators. One of these, interferon (IFN)β, a Type I IFN, plays a protective role in MS and EAE. We have previously shown that intrathecal administration of selected TLR ligands induced IFNβ and infiltration of blood-derived myeloid cells into the central nervous system (CNS), and suppressed E…

Severe dysautonomia in glycine receptor antibody-positive progressive encephalomyelitis with rigidity and myoclonus (PERM): A case report.

Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a severe form of stiff-person spectrum disorder. We report a 59-year-old man who presented with progressive encephalomyelitis causing diplopia, bulbar palsy, severe dysautonomia, followed by stiffness and myoclonic cluster. Laboratory tests showed mild pleocytosis, with markedly elevated plasma levels of norepinephrine, epinephrine, and arginine vasopressin. Glycine-receptor antibodies were identified in both serum and CSF. Despite a poor response to methylprednisolone, immunoglobulins, and plasma exchange, α-blocker stabilize…

Ross River Virus Immune Evasion Strategies and the Relevance to Post-viral Fatigue, and Myalgic Encephalomyelitis Onset.

Ross River virus (RRV) is an endemic Australian arbovirus, and member of the Alphavirus family that also includes Chikungunya virus (CHIK). RRV is responsible for the highest prevalence of human disease cases associated with mosquito-borne transmission in Australia, and has long been a leading suspect in cases of post-viral fatigue syndromes, with extrapolation of this link to Myalgic Encephalomyelitis (ME). Research into RRV pathogenesis has revealed a number of immune evasion strategies, impressive for a virus with a genome size of 12 kb (plus strand RNA), which resonate with insights into v…

A Soluble Epoxide Hydrolase Inhibitor, 1-TrifluoromethoxyPhenyl-3-(1-Propionylpiperidin-4-yl) Urea, Ameliorates Experimental Autoimmune Encephalomyelitis.

Polyunsaturated fatty acids (PUFAs) are essential FAs for human health. Cytochrome P450 oxygenates PUFAs to produce anti-inflammatory and pa … piperidin-4-yl) urea (TPPU), in an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Prophylactic TPPU treatment significantly ameliorated EAE without affecting circulating white blood cell counts. TPPU accumulated in the spinal cords (SCs), which was correlated with plasma TPPU concentration. Targeted lipidomics in EAE SCs a …

Targeted Blood Brain Barrier Opening With Focused Ultrasound Induces Focal Macrophage/Microglial Activation in Experimental Autoimmune Encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a model of multiple sclerosis (MS). EAE reflects important histopathological hallmarks, dissemination, and diversity of the disease, but has only moderate reproducibility of clinical and histopathological features. Focal lesions are less frequently observed in EAE than in MS, and can neither be constrained to specific locations nor timed to occur at a pre-specified moment. This renders difficult any experimental assessment of the pathogenesis of lesion evolution, including its inflammatory, degenerative (demyelination and axonal degeneration),…

Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause chronic and acute disease. Postacute sequelae of SARS-CoV-2 infection (PASC) include injury to the lungs, heart, kidneys, and brain that may produce a variety of symptoms. PASC also includes a post-coronavirus disease 2019 (COVID-19) syndrome ('long COVID') with features that can follow other acute infectious diseases and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Here we summarize what is known about the pathogenesis of ME/CFS and of 'acute' COVID-19, and we speculate that the pathogenesis of post-COVID-1…

Circulating leptin levels in patients with myalgic encephalomyelitis, chronic fatigue syndrome or fibromyalgia: a systematic review protocol.

OBJECTIVE: The objective of the review is to evaluate circulating levels of leptin in people diagnosed with myalgic encephalomyelitis chronic fatigue syndrome or fibromyalgia syndrome and to investigate the differences compared with healthy controls. INTRODUCTION: Myalgic encephalomyelitis chronic fatigue syndrome is a condition that has major symptoms, including self-reported fatigue, post-exertional malaise, and unexplained pain across the body. The widespread pain is measured in a systematic way and is often referred to as fibromyalgia. The two disorders have many similarities, but their a…

Limiting Neuronal Nogo Receptor 1 Signaling during Experimental Autoimmune Encephalomyelitis Preserves Axonal Transport and Abrogates Inflammatory Demyelination.

We previously identified that ngr1 allele deletion limits the severity of experimental autoimmune encephalomyelitis (EAE) by preserving axonal integrity. However, whether this favorable outcome observed in EAE is a consequence of an abrogated neuronal-specific pathophysiological mechanism, is yet to be defined. Here we show that, Cre-loxP-mediated neuron-specific deletion of ngr1 preserved axonal integrity, whereas its re-expression in ngr1-/- female mice potentiated EAE-axonopathy. As a corollary, myelin integrity was preserved under Cre deletion in ngr1flx/flx , retinal ganglion cell axons w…