SOX10-Mediated Regulation of Enteric Glial Phenotype in vitro and its Relevance for Neuroinflammatory Disorders.

The transcription factor SOX10 is a key regulator of myelinated glial cell phenotype and function, with a known role in multiple sclerosis (MS). SOX10 is also expressed in enteric glial cells (EGC) within the gut, yet its regulatory functions in EGC remain poorly understood. This study aimed to identify SOX10 target genes that influence EGC phenotype and may have implications for MS.

Modulator of VRAC Current 1 Is a Potential Target Antigen in Multiple Sclerosis.

Background And Objectives: Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the CNS. Highlighted by the success of B-cell-depleting therapies such as the monoclonal anti-CD20 antibodies rituximab, ocrelizumab, and ofatumumab, B cells have been shown to play a central role in the immunopathology of the disease. Yet, the target antigens of the pathogenic B-cell response in MS remain unclear.

MRI-based morphometric structural changes correlate with histopathology in experimental autoimmune encephalomyelitis.

Background And Objectives: Magnetic resonance imaging (MRI) and neurohistopathology are important correlates for evaluation of disease progression in multiple sclerosis (MS). Here we used experimental autoimmune encephalomyelitis (EAE) as an animal model of MS to determine the correlation between clinical EAE severity, MRI and histopathological parameters.

Methods: N = 11 female C57BL/6J mice were immunized with human myelin oligodendrocyte glycoprotein 1-125, while N = 9 remained non-immunized.

Fibroblast growth factor 8 promotes in vitro neurite outgrowth of placode-derived petrosal and nodose ganglia to varying degrees.

Fibroblast growth factors (FGFs) are required for the specification and formation of the epibranchial placodes, which give rise to the distal part of the cranial sensory ganglia. However, it remains unclear whether FGFs play a role in regulating the neurite outgrowth of the epibranchial placode-derived ganglia during further development. Previous studies have shown that Fibroblast growth factor 8 (FGF8) promotes neurite outgrowth from the statoacoustic ganglion in vitro.

Dietary galactose exacerbates autoimmune neuroinflammation advanced glycation end product-mediated neurodegeneration.

Background: Recent studies provide increasing evidence for a relevant role of lifestyle factors including diet in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). While the intake of saturated fatty acids and elevated salt worsen the disease outcome in the experimental model of MS by enhanced inflammatory but diminished regulatory immunological processes, sugars as additional prominent components in our daily diet have only scarcely been investigated so far. Apart from glucose and fructose, galactose is a common sugar in the so-called Western diet.

The mitochondrial protease PARL is required for spermatogenesis.

Mitochondrial function plays an important role in the maintenance of male fertility. However, the mechanisms underlying mitochondrial defect-related infertility remain mostly unclear. Here we show that a deficiency of PARL (Parl), a mitochondrial protease, causes complete arrest of spermatogenesis during meiosis I.

Immune monitoring of SARS-CoV-2-specific T cell and B cell responses in patients with multiple sclerosis treated with ocrelizumab.

Introduction: Since the development of the coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), there has been significant interest in determining the effectiveness of SARS-CoV-2 vaccines in patients under immunomodulatory or immunosuppressive therapies. The aim of this study was to evaluate the impact of ocrelizumab, a monoclonal anti-CD20 antibody, on SARS-CoV-2-specific T cell and B cell responses in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: To this end, peripheral blood mononuclear cells (PBMCs) were isolated from = 23 patients with RRMS.

A Dual Role of Osteopontin in Modifying B Cell Responses.

The occurrence of B cell aggregates within the central nervous system (CNS) has prompted the investigation of the potential sources of pathogenic B cell and T cell responses in a subgroup of secondary progressive multiple sclerosis (MS) patients. Nevertheless, the expression profile of molecules associated with these aggregates and their role in aggregate development and persistence is poorly described. Here, we focused on the expression pattern of osteopontin (OPN), which is a well-described cytokine, in MS brain tissue.

The prevalence of IgG antibodies against milk and milk antigens in patients with multiple sclerosis.

Introduction: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). The pathophysiology of MS is complex and is said to be influenced by multiple environmental determinants, including diet. We and others have previously demonstrated how consumption of bovine milk can aggravate disease severity in MS patients, which can be explained by molecular mimicry between milk antigens and those expressed within the CNS.

Pressure-Dependent Elevation of Vasoactive Intestinal Peptide Level in Chicken Choroid.

Purpose: Autonomic control is important in maintaining ocular integrity. As recent data suggested that intrinsic choroidal neurons (ICN), an intrinsic choroidal autonomic control, may regulate choroidal thickening via release of the vasodilative vasoactive intestinal peptide (VIP), it was the aim of the study to investigate the level of choroidal VIP (VIP) in the presence of an increased atmospheric pressure in a chicken model.

Methods: Chicken choroidal whole mounts were exposed to ambient pressure ( = 20) and 40 mm Hg ( = 20) in a PC-controlled, open chamber system for 24 and 72 h, respectively.

Impact of the Voltage-Gated Calcium Channel Antagonist Nimodipine on the Development of Oligodendrocyte Precursor Cells.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While most of the current treatment strategies focus on immune cell regulation, except for the drug siponimod, there is no therapeutic intervention that primarily aims at neuroprotection and remyelination. Recently, nimodipine showed a beneficial and remyelinating effect in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS.

Dynamic study of the finger interphalangeal joint volar plate-motion analysis with magnetic resonance cinematography and histologic comparison.

Objective: We aimed to further improve knowledge about volar plate (VP) motion of the finger proximal interphalangeal joint (PIP), by analyzing the dynamic VP shape during a full range of finger flexion using magnetic resonance cinematography of the fingers (MRCF), and to compare the results with anatomical cross sections from cadaver specimens.

Materials And Methods: The dynamic sagittal VP shape was visualized with MRCF in a total number of 23 healthy volunteers. The length, angle, and thickness as well as the contact length of the VP to the PIP joint base were measured.

The presence of cerebellar B cell aggregates is associated with a specific chemokine profile in the cerebrospinal fluid in a mouse model of multiple sclerosis.

Background: The presence of meningeal ectopic lymphoid structures (ELS) in a subgroup of patients diagnosed with secondary progressive multiple sclerosis (SPMS) corresponds to a pronounced cortical inflammation and an aggravated disease course. In MP4-induced experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), B cell aggregates develop in the central nervous system (CNS) in the chronic stage of the disease. Therefore, the model is suitable for studying key molecules of ELS development and maintenance.

Impact of Siponimod on Enteric and Central Nervous System Pathology in Late-Stage Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Although immune modulation and suppression are effective during relapsing-remitting MS, secondary progressive MS (SPMS) requires neuroregenerative therapeutic options that act on the CNS. The sphingosine-1-phosphate receptor modulator siponimod is the only approved drug for SPMS.

Antibody Levels Poorly Reflect on the Frequency of Memory B Cells Generated following SARS-CoV-2, Seasonal Influenza, or EBV Infection.

The scope of immune monitoring is to define the existence, magnitude, and quality of immune mechanisms operational in a host. In clinical trials and praxis, the assessment of humoral immunity is commonly confined to measurements of serum antibody reactivity without accounting for the memory B cell potential. Relying on fundamentally different mechanisms, however, passive immunity conveyed by pre-existing antibodies needs to be distinguished from active B cell memory.

Identification of a novel role for matrix metalloproteinase-3 in the modulation of B cell responses in multiple sclerosis.

There has been a growing interest in the presence and role of B cell aggregates within the central nervous system of multiple sclerosis patients. However, very little is known about the expression profile of molecules associated with these aggregates and how they might be influencing aggregate development or persistence in the brain. The current study focuses on the effect of matrix metalloproteinase-3, which is associated with B cell aggregates in autopsied multiple sclerosis brain tissue, on B cells.

Nimodipine Exerts Beneficial Effects on the Rat Oligodendrocyte Cell Line OLN-93.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS). Therapy is currently limited to drugs that interfere with the immune system; treatment options that primarily mediate neuroprotection and prevent neurodegeneration are not available. Here, we studied the effects of nimodipine on the rat cell line OLN-93, which resembles young mature oligodendrocytes.

Effects of a Fully Humanized Type II Anti-CD20 Monoclonal Antibody on Peripheral and CNS B Cells in a Transgenic Mouse Model of Multiple Sclerosis.

Successful therapy with anti-CD20 monoclonal antibodies (mAbs) has reinforced the key role of B cells in the immunopathology of multiple sclerosis (MS). This study aimed to determine the effects of a novel class of anti-CD20 mAbs on vascular and extravascular central nervous system (CNS)-infiltrating B cells in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Male hCD20xhIgR3 mice and wild-type C57BL/6 (B6) mice were immunized with human myelin oligodendrocyte glycoprotein (MOG) to induce EAE.

Antibody cross-reactivity between casein and myelin-associated glycoprotein results in central nervous system demyelination.

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease of the central nervous system (CNS) with a high socioeconomic relevance. The pathophysiology of MS, which is both complex and incompletely understood, is believed to be influenced by various environmental determinants, including diet. Since the 1990s, a correlation between the consumption of bovine milk products and MS prevalence has been debated.

Affinity Tag Coating Enables Reliable Detection of Antigen-Specific B Cells in Immunospot Assays.

Assessment of humoral immunity to SARS-CoV-2 and other infectious agents is typically restricted to detecting antigen-specific antibodies in the serum. Rarely does immune monitoring entail assessment of the memory B-cell compartment itself, although it is these cells that engage in secondary antibody responses capable of mediating immune protection when pre-existing antibodies fail to prevent re-infection. There are few techniques that are capable of detecting rare antigen-specific B cells while also providing information regarding their relative abundance, class/subclass usage and functional affinity.

MRI of Finger Pulleys at 7T-Direct Characterization of Pulley Ruptures in an Ex Vivo Model.

The aim of this study was to evaluate 7 Tesla (7T) magnetic resonance imaging (MRI) for direct visualization and specific characterization of the finger flexor pulleys A2, A3, and A4 before and after ex vivo pulley rupture. Thirty fingers of human cadavers were examined before and after pulley disruption with a 26 min clinical 7T pulse sequence protocol. Images were assessed by two experienced radiologists for the presence of pulley rupture.

Mice Heterozygous for the Sodium Channel Scn8a (Nav1.6) Have Reduced Inflammatory Responses During EAE and Following LPS Challenge.

Voltage gated sodium (Nav) channels contribute to axonal damage following demyelination in experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis (MS). The Nav1.6 isoform has been implicated as a primary contributor in this process.

Murine Esophagus Expresses Glial-Derived Central Nervous System Antigens.

Multiple sclerosis (MS) has been considered to specifically affect the central nervous system (CNS) for a long time. As autonomic dysfunction including dysphagia can occur as accompanying phenomena in patients, the enteric nervous system has been attracting increasing attention over the past years. The aim of this study was to identify glial and myelin markers as potential target structures for autoimmune processes in the esophagus.

B-Cell Activity Predicts Response to Glatiramer Acetate and Interferon in Relapsing-Remitting Multiple Sclerosis.

Objective: We investigated the predictive value of the enzyme-linked immunospot technique (ELISPOT) in identifying patients with relapsing-remitting multiple sclerosis (RRMS) who will respond to treatment with glatiramer acetate (GA) or interferon-β (IFN-β), based on the brain-reactive B-cell activity of peripheral blood cells.

Methods: In this retrospective, cross-sectional, real-world multicenter study, we identified patients with RRMS in the NeuroTransData MS registry and stratified them based on their documented treatment response (relapse-free in the first 12 months of treatment) to GA or IFN-β. The GA group comprised 73 patients who responded to GA and 35 nonresponders.