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Forsythoside B улучшает нейроинфламму через ингибирование NLRP3 воспаления глиальных клеток в экспериментальной аутоиммунной энцефаломиелитной мыши.

Нейроинфламмация, спровоцированная глиарными клетками, играет решающую роль в обезвоживании в экспериментальной аутоиммунной энцефаломиелите (EAE) - модели множественного склероза (MS). Forsythoside B (FTS·B) — натуральный фенилатаноидный гликосайд, изолированный от сушеных фруктов, и листья Forsythia sessensa (Thunb.) Val, имеют антиоксидантные, антиапоптотические и противовоспалительные свойства. Однако в настоящее время не имеется ни доклада, ни исследования по вопросу об эффективности лечения ЭССХ. Цель этого исследования заключалась в изучении нейрозащитных свойств (FTS·B) ЭССЭ и выявлени

Совпадение в аннотации оригинала
Neuroinflammation mediated by glial cells plays a crucial role in demyelination in experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis (MS) model. Forsythoside B (FTS·B), a natural phenylethanoid glycoside isolated from the dried fruits and leaves of Forsythia suspensa (Thunb.) Vahl, has been found to have antioxidant, anti-apoptotic, and a…

Serum from Myalgic encephalomyelitis/chronic fatigue syndrome patients causes loss of coherence in cellular circadian rhythms.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disabling disorder characterized by disrupted daily patterns of activity, sleep, and physiology. Past studies in ME/CFS patients have examined circadian rhythms, suggested that desynchronization between central and peripheral rhythms may be an important pathological feature, and identified associated changes in post-inflammatory cytokines such as transforming growth factor beta (TGFB). However, no previous studies have examined circadian rhythms in ME/CFS using cellular models or studied the role of cytokines on circadian rhythms…

Case report: A case of acute disseminated encephalomyelitis after SARS-CoV-2 infection in pediatric patients.

INTRODUCTION: Since the beginning, there has been enough evidence about the multi-systematic involvement of the coronavirus disease 2019 (CO … as seizure, coma, encephalitis, demyelinating disorders, and aseptic meningitis. Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system. Typically, it presents in childhood and occurs 1 or 2 weeks after infection or vaccination. CASE PRESENTATION: We present the case of a 12-year-old boy who developed ADE …

Protocol to assess the tolerogenic properties of adoptively transferred dendritic cells during murine experimental autoimmune encephalomyelitis.

By their capacity to induce peripheral T cell tolerance, dendritic cells (DCs) present a promising target cell and therapeutic strategy for treatment of several autoimmune diseases including multiple sclerosis (MS). This protocol describes how to determine the tolerogenic capacities of DCs in the context of the murine MS model, experimental autoimmune encephalomyelitis (EAE). We provide a step-by-step instruction for EAE induction, antigen-loaded bone-marrow-derived-DC (BM-DC) generation, adoptive cell transfer, and analysis of DC-mediated changes in regulatory T cell populations. For complete…

Drug repurposing of ilepcimide that ameliorates experimental autoimmune encephalomyelitis via restricting inflammatory response and oxidative stress.

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS) that remains incurable. Herein, we demonstrated that ilepcimide (Antiepilepsirine), an antiepileptic drug used for decades, protects mice from experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Our studies found that ilepcimide treatment effectively ameliorates demyelination, blood-brain barrier leakage and infiltration of CD4+ and CD8+ T cells in EAE mice. On the one hand, ilepcimide can inhibit dihydroorotate dehydrogenase (DHODH), an important therapeutic target for MS…

Transient Myelin Oligodendrocyte Glycoprotein Antibody-positive Acute Disseminated Encephalomyelitis Following Influenza A Infection: A Rare Case.

Acute disseminated encephalomyelitis (ADEM) is an uncommon disease generally with a preceding history of infectious illness. Here, we report a rare case of ADEM following influenza A infection with transient detection of anti-myelin oligodendrocyte glycoprotein (MOG) antibody in a young male patient who presented with extensive demyelination of brain and spinal cord, likely the result of dysregulated immune response from previous influenza A infection. The patient presented to the emergency with urinary retention and progressive ascending weakness of lower limbs. Magnetic resonance imaging (MR…

Bcl6 modulates innate immunity by controlling macrophage activity and plays critical role in experimental autoimmune encephalomyelitis.

The B-cell CLL/lymphoma 6 (Bcl6) oncogenic repressor is a master regulator of humoral immunity and B-cell lymphomagenesis. Although much research has focused on its regulation and function of GC B cells and T cells, the role of Bcl6 in regulating the functions of innate immunity is not well defined. Here, we demonstrated that EAE is exacerbated in LysM Cre+/- Bcl6fl/fl mice. Although other cells such as neutrophils might be involved in this conditional mutant mouse model, we found that the disease pathology is mainly associated with a biased M1 macrophage activity and an enhanced encephalitoge

LRR domain of NLRX1 protein delivery by dNP2 inhibits T cell functions and alleviates autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a demyelinating inflammatory disease of the central nervous system (CNS), which is a chronic progressive disease and is caused by uncontrolled activation of myelin antigen specific T cells. It has high unmet medical needs due to the difficulty of efficient drug delivery into the CNS to control tissue inflammation. In this study, we demonstrate that a fusion protein of NOD-like receptor family member X1 (NLRX1) and blood brain barrier (BBB)-permeable peptide, dNP2 ameliorates experimental autoimmune encephalomyelitis (EAE). Methods: We purified recombinant LRR or NBD …

Arsenic trioxide ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice by inducing CD4+ T cell apoptosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by severe white matter demyelination. Because of its complex pathogenesis, there is no definite cure for MS. Experimental autoimmune encephalomyelitis (EAE) is an ideal animal model for the study of MS. Arsenic trioxide (ATO) is an ancient Chinese medicine used for its therapeutic properties with several autoimmune diseases. It is also used to inhibit acute immune rejection due to its anti-inflammatory and immunosuppressive properties. However, it is unclear whether ATO has a therapeut…

The association of SARS-CoV-2 infection and acute disseminated encephalomyelitis without prominent clinical pulmonary symptoms.

• We describe a patient with acute disseminated encephalitis and COVID-19. • CNS manifestations primarily occurred without evident pulmonary symptoms. • Brain MRI of the patient indicated diffuse confluent white matter hyperintensities. • The patient initially responded to steroids but lastly, died of status epilepticus. • The occurrence of acute disseminated encephalitis may have been immune-mediated.

Disrupting Myelin-Specific Th17 Cell Gut Homing Confers Protection in an Adoptive Transfer Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is a common autoimmune disease of the CNS. Although an association between MS and inflammatory bowel diseases is observed, the link connecting intestinal immune responses and neuroinflammation remains unclear. Here we show that encephalitogenic Th17 cells infiltrate the colonic lamina propria before neurological symptom development in two murine MS models, active and adoptive transfer experimental autoimmune encephalomyelitis (EAE). Specifically targeting Th17 cell intestinal homing by blocking the α4β7-integrin and its ligand MAdCAM-1 pathway impairs T cell migration t…

Auto-Reactive Th17-Cells Trigger Obsessive-Compulsive-Disorder Like Behavior in Mice With Experimental Autoimmune Encephalomyelitis.

Th17-lymphocytes are well known for their deleterious role in autoimmunity. But does the notoriety of this repertoire extend beyond autoimmunity? In the present study we employed experimental autoimmune encephalomyelitis as model system to study the role auto-reactive Th17 cells in neuropsychiatric disorders. The mice with experimental autoimmune encephalomyelitis exhibited exaggerated grooming activity. The observed behavioral anomaly resembled obsessive compulsive disorder (OCD) upon analysis of grooming microstructure, induced grooming, marble burying and nestlet shredding. The observed OCD…

The Interleukin (IL)-23/T helper (Th)17 Axis in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis.

T helper (Th)17 cells are responsible for host defense against fungi and certain extracellular bacteria but have also been reported to play a role in a variety of autoimmune diseases. Th17 cells respond to environmental cues, are very plastic, and might also be involved in tissue homeostasis and regeneration. The imprinting of pathogenic properties in Th17 cells in autoimmunity seems highly dependent on interleukin (IL)-23. Since Th17 cells were first described in experimental autoimmune encephalomyelitis, they have been suggested to also promote tissue damage in multiple sclerosis (MS). Indee…

Deficient arginase II expression without alteration in arginase I expression attenuated experimental autoimmune encephalomyelitis in mice.

In the past there have been a multitude of studies that ardently support the role of arginase II (Arg II) in vascular and endothelial disorders; however, the regulation and function of Arg II in autoimmune diseases has thus far remained unclear. Here we report that a global Arg II null mutation in mice suppressed experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. During EAE, both Arg I and Arg II were induced in spinal cords, but only Arg II was induced in spleens and splenic dendritic cells (DCs). DC activation by lipopolysaccharide (LPS), CD40L or TLR8 ag…

Deconstructing post-exertional malaise in myalgic encephalomyelitis/ chronic fatigue syndrome: A patient-centered, cross-sectional survey.

BACKGROUND: Post-exertional malaise (PEM) is considered to be the hallmark characteristic of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). Yet, patients have rarely been asked in formal studies to describe their experience of PEM. OBJECTIVES: To describe symptoms associated with and the time course of PEM. METHODS: One hundred and fifty subjects, diagnosed via the 1994 Fukuda CFS criteria, completed a survey concerning 11 symptoms they could experience after exposure to two different types of triggers. We also inquired about onset and duration of PEM and included space for su…

Improvement of severe myalgic encephalomyelitis/chronic fatigue syndrome symptoms following surgical treatment of cervical spinal stenosis.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a potentially disabling disorder. Little is known about the contributors to severe forms of the illness. We describe three consecutive patients with severe ME/CFS whose symptoms improved after recognition and surgical management of their cervical spinal stenosis. METHODS: All patients satisfied clinical criteria for ME/CFS and orthostatic intolerance, and were later found to have cervical spinal stenosis. Overall function was assessed before and after surgery using the Karnofsky score and the SF-36 physical function su…

Examining clinical similarities between myalgic encephalomyelitis/chronic fatigue syndrome and D-lactic acidosis: a systematic review.

BACKGROUND: The pursuit for clarity in diagnostic and treatment pathways for the complex, chronic condition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) continues. This systematic review raises a novel question to explore possible overlapping aetiology in two distinct conditions. Similar neurocognitive symptoms and evidence of D-lactate producing bacteria in ME/CFS raise questions about shared mechanisms with the acute condition of D-lactic acidosis (D-la). METHODS: D-la case reports published between 1965 and March 2016 were reviewed for episodes describing both neurologica…

Intravenous Injection of Myelin Oligodendrocyte Glycoprotein-coated PLGA Microparticles Have Tolerogenic Effects in Experimental Autoimmune Encephalomyelitis.

The abnormal function of the T lymphocytes causes a range of autoimmune diseases, particularly multiple sclerosis; hence, several methods ha … injected to six groups of C57BL/6 mice one week before the induction of the experimental autoimmune encephalomyelitis (EAE) intravenously or subcutaneously; one group was considered as control; finally, immunologic responses including delayed-type hypersensitivity (DTH) response and lymphocyte proliferation were investigated. The results showed that the intravenous …

Obeticholic acid, a synthetic bile acid agonist of the farnesoid X receptor, attenuates experimental autoimmune encephalomyelitis.

Bile acids are ligands for the nuclear hormone receptor, farnesoid X receptor (FXR). The bile acid-FXR interaction regulates bile acid synthesis, transport, and cholesterol metabolism. Recently, bile acid-FXR regulation has been reported to play an integral role in both hepatic and intestinal inflammation, and in atherosclerosis. In this study, we found that FXR knockout mice had more disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Obeticholic acid (6α-ethyl-chenodeoxycholic acid, 6-ECDCA), a synthetic FXR agonist, is an orally a…

Central Nervous System Demyelination and Remyelination is Independent from Systemic Cholesterol Level in Theiler's Murine Encephalomyelitis.

High dietary fat and/or cholesterol intake is a risk factor for multiple diseases and has been debated for multiple sclerosis. However, cholesterol biosynthesis is a key pathway during myelination and disturbances are described in demyelinating diseases. To address the possible interaction of dyslipidemia and demyelination, cholesterol biosynthesis gene expression, composition of the body's major lipid repositories and Paigen diet-induced, systemic hypercholesterolemia were examined in Theiler's murine encephalomyelitis (TME) using histology, immunohistochemistry, serum clinical chemistry, mic…