Oral vancomycin treatment suppresses gut trypsin activity and preserves intestinal barrier function during EAE.

Studies have reported increased intestinal permeability in multiple sclerosis (MS) patients and its mouse model experimental autoimmune encephalomyelitis (EAE). However, the mechanisms driving increased intestinal permeability that in turn exacerbate neuroinflammation during EAE remain unclear. Here we showed that vancomycin preserved the integrity of the intestinal barrier, while also suppressing gut trypsin activity, enhancing the relative abundance of specific and ameliorating disease during EAE.

The OSCAR-MP Consensus Criteria for Quality Assessment of Retinal Optical Coherence Tomography Angiography.

Background And Objectives: Optical coherence tomography angiography (OCTA) is a noninvasive high-resolution imaging technique for assessing the retinal vasculature and is increasingly used in various ophthalmologic, neuro-ophthalmologic, and neurologic diseases. To date, there are no validated consensus criteria for quality control (QC) of OCTA. Our study aimed to develop criteria for OCTA quality assessment.

Human NMDAR autoantibodies disrupt excitatory-inhibitory balance, leading to hippocampal network hypersynchrony.

Anti-NMDA receptor autoantibodies (NMDAR-Abs) in patients with NMDAR encephalitis cause severe disease symptoms resembling psychosis and cause cognitive dysfunction. After passive transfer of patients' cerebrospinal fluid or human monoclonal anti-GluN1-autoantibodies in mice, we find a disrupted excitatory-inhibitory balance resulting from CA1 neuronal hypoexcitability, reduced AMPA receptor (AMPAR) signaling, and faster synaptic inhibition in acute hippocampal slices. Functional alterations are also reflected in widespread remodeling of the hippocampal proteome, including changes in glutamatergic and GABAergic neurotransmission.

NMOSD IgG Impact Retinal Cells in Murine Retinal Explants.

Neuromyelitis optica spectrum disorders (NMOSD) are chronic inflammatory diseases of the central nervous system, characterized by autoantibodies against aquaporin-4. The symptoms primarily involve severe optic neuritis and longitudinally extensive transverse myelitis. Although the disease progression is typically relapse-dependent, recent studies revealed retinal neuroaxonal degeneration unrelated to relapse activity, potentially due to anti-aquaporin-4-positive antibodies interacting with retinal glial cells such as Müller cells.

Therapy challenges for NMOSD in a patient with HIV.

Neuromyelitis optica spectrum disorder (NMOSD) in people living with HIV (PLWH) is rare and its management can be difficult. Here we report a case of an HIV patient with bilateral vision loss, who was diagnosed with AQP4-IgG-positive NMOSD in 2020 during the COVID-19 pandemic. Rituximab treatment was initiated after attack therapy with corticosteroids and plasma exchange.

A genome-wide in vivo CRISPR screen identifies essential regulators of T cell migration to the CNS in a multiple sclerosis model.

Multiple sclerosis (MS) involves the infiltration of autoreactive T cells into the CNS, yet we lack a comprehensive understanding of the signaling pathways that regulate this process. Here, we conducted a genome-wide in vivo CRISPR screen in a rat MS model and identified 5 essential brakes and 18 essential facilitators of T cell migration to the CNS. While the transcription factor ETS1 limits entry to the CNS by controlling T cell responsiveness, three functional modules, centered around the adhesion molecule α4-integrin, the chemokine receptor CXCR3 and the GRK2 kinase, are required for CNS migration of autoreactive CD4 T cells.

Factors associated with depressive mood at the onset of multiple sclerosis - an analysis of 781 patients of the German NationMS cohort.

Background: Depression has a major impact on the disease burden of multiple sclerosis (MS). Analyses of overlapping MS and depression risk factors [smoking, vitamin D (25-OH-VD) and Epstein-Barr virus (EBV) infection] and sex, age, disease characteristics and neuroimaging features associated with depressive symptoms in early MS are scarce.

Objectives: To assess an association of MS risk factors with depressive symptoms within the German NationMS cohort.

Inner Retinal Layer Changes Reflect Changes in Ambulation Score in Patients with Primary Progressive Multiple Sclerosis.

The establishment of surrogate markers to detect disability progression in persons with multiple sclerosis (PwMS) is important to improve monitoring of clinical deterioration. Optical coherence tomography (OCT) could be such a tool. However, sufficient longitudinal data of retinal neuroaxonal degeneration as a marker of disease progression exist only for PwMS with a relapsing-remitting course (RRMS) so far.

Pairing of single-cell RNA analysis and T cell antigen receptor profiling indicates breakdown of T cell tolerance checkpoints in atherosclerosis.

Atherosclerotic plaques form in the inner layer of arteries triggering heart attacks and strokes. Although T cells have been detected in atherosclerosis, tolerance dysfunction as a disease driver remains unexplored. Here we examine tolerance checkpoints in atherosclerotic plaques, artery tertiary lymphoid organs and lymph nodes in mice burdened by advanced atherosclerosis, via single-cell RNA sequencing paired with T cell antigen receptor sequencing.

Visualizing the activation of encephalitogenic T cells in the ileal lamina propria by in vivo two-photon imaging.

Autoreactive encephalitogenic T cells exist in the healthy immune repertoire but need a trigger to induce CNS inflammation. The underlying mechanisms remain elusive, whereby microbiota were shown to be involved in the manifestation of CNS autoimmunity. Here, we used intravital imaging to explore how microbiota affect the T cells as trigger of CNS inflammation.

Neurons on tape: Automated Tape Collecting Ultramicrotomy-mediated volume EM for targeting neuropathology.

In this chapter, we review Automated Tape Collecting Ultramicrotomy (ATUM), which, among other array tomography methods, substantially simplified large-scale volume electron microscopy (vEM) projects. vEM reveals biological structures at nanometer resolution in three dimensions and resolves ambiguities of two-dimensional representations. However, as the structures of interest-like disease hallmarks emerging from neuropathology-are often rare but the field of view is small, this can easily turn a vEM project into a needle in a haystack problem.

Early molecular layer interneuron hyperactivity triggers Purkinje neuron degeneration in SCA1.

Toxic proteinaceous deposits and alterations in excitability and activity levels characterize vulnerable neuronal populations in neurodegenerative diseases. Using in vivo two-photon imaging in behaving spinocerebellar ataxia type 1 (Sca1) mice, wherein Purkinje neurons (PNs) degenerate, we identify an inhibitory circuit element (molecular layer interneurons [MLINs]) that becomes prematurely hyperexcitable, compromising sensorimotor signals in the cerebellum at early stages. Mutant MLINs express abnormally elevated parvalbumin, harbor high excitatory-to-inhibitory synaptic density, and display more numerous synaptic connections on PNs, indicating an excitation/inhibition imbalance.

Features of Isoforms of Human Soluble TACI.

The BAFF/APRIL-system with the two cytokines BAFF and APRIL and their three receptors, transmembrane activator and CAML interactor (TACI), BAFF receptor, and B-cell maturation Ag, is important for B cell maintenance. The BAFF/APRIL system is a therapeutic target in B cell-derived malignancies and autoimmune diseases. However, unexpected outcomes of clinical trials with atacicept (TACI-Fc) underline our incomplete understanding of this system.

Age-dependent retinal neuroaxonal degeneration in children and adolescents with Leber hereditary optic neuropathy under idebenone therapy.

Background: The aim of this study was to investigate the neuroretinal structure of young patients with Leber hereditary optic neuropathy (LHON).

Methods: For this retrospective cross-sectional analysis, the peripapillary retinal nerve fiber layer (pRNFL) thickness and the macular retinal layer volumes were measured by optical coherence tomography. Patients aged 12 years or younger at disease onset were assigned to the childhood-onset (ChO) group and those aged 13-16 years to the early teenage-onset (eTO) group.

Remyelination by surviving oligodendrocytes is inefficient in the inflamed mammalian cortex.

In multiple sclerosis, an inflammatory attack results in myelin loss, which can be partially reversed by remyelination. Recent studies suggest that mature oligodendrocytes could contribute to remyelination by generating new myelin. Here, we show that in a mouse model of cortical multiple sclerosis pathology, surviving oligodendrocytes can indeed extend new proximal processes but rarely generate new myelin internodes.

Retrospective cohort study to devise a treatment decision score predicting adverse 24-month radiological activity in early multiple sclerosis.

Background: Multiple sclerosis (MS) is a chronic neuroinflammatory disease affecting about 2.8 million people worldwide. Disease course after the most common diagnoses of relapsing-remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) is highly variable and cannot be reliably predicted.