Neuromyelitis optica spectrum disorder (NMOSD) encompasses inflammatory demyelinating CNS conditions. Patients negative for aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) antibodies are classified as double seronegative (DN).

Bone marrow-derived mesenchymal stem cells (BMSCs) are promising candidates for treating autoimmune diseases like multiple sclerosis (MS) due to their ability to differentiate into multiple lineages and their immunomodulatory properties. However, the immunomodulatory capacity of BMSCs is highly adaptable, and primarily regulated by inflammatory factors. In this study, we evaluated the therapeutic effectiveness of BMSCs in dexamethasone (DEX)-pretreated experimental autoimmune encephalomyelitis (EAE) mice. Our results demonstrated a significant interaction between DEX and BMSCs. In contrast to their effect in non-pretreated mice, BMSCs administration in DEX-pretreated EAE mice resulted in a significant increase in infiltrating CD4 T cells and a concomitant decrease in regulatory T (Treg) cell populations in the central nerves system, which likely resulted from DEX-induced changes in the peripheral immune microenvironment. Our findings in the EAE model indicate that the immune microenvironment established by DEX pretreatment is detrimental to the efficacy of BMSC therapy. This preclinical evidence suggests that evaluating the peripheral immune status may be a critical consideration for future clinical studies of MSC treatment in MS.

Transitioning from sphingosine-1-phosphate modulators, such as fingolimod, to anti-CD20 therapies is common in patients with multiple sclerosis due to suboptimal disease control, progression, or family planning. However, the optimal washout period remains unclear, and cases of disease activity rebound following discontinuation of fingolimod have been documented. We present the case of a 43-year-old woman who developed severe rebound disease activity after transitioning from fingolimod to ofatumumab, despite a washout period of 28 days. The patient experienced a new lesion and neuropsychological impairment, which improved after treatment with high-dose methylprednisolone. Literature review highlights the complexity of factors influencing rebound, including washout duration, lymphocyte count, and disease control during fingolimod therapy. Evidence suggests that initiating ofatumumab treatment without a prolonged washout period may mitigate rebound risk.

The use of immune checkpoint inhibitors (ICIs), a class of oncologic therapies that enhance anti-tumor immunity, may be complicated by the occurrence of neurologic immune-related adverse events (n-irAEs). ICI-induced neurotoxicities predominantly affect the peripheral nervous system, manifesting as myositis, polyradiculoneuropathies and cranial neuropathies and, less frequently, involve the central nervous system, typically as encephalitis or myelitis. The diagnosis of n-irAEs relies on the exclusion of alternative etiologies - such as cancer dissemination, chemotherapy-induced neurotoxicities, and neuroinfections - and the recognition of specific clinical syndromes. Neuroradiological investigations, particularly magnetic resonance imaging (MRI), play a crucial role in ruling out differential diagnosis, mainly cancer dissemination. Furthermore, MRI can support the clinical suspicious of an immune-mediated process by demonstrating indirect signs of neuroinflammation, including tissue edema and gadolinium enhancement. Nuclear medicine techniques, such as position emission tomography and scintigraphy, may also aid in the assessment of ICI-induced encephalitis and parkinsonism. Despite the recognized clinical relevance of imaging investigations in the diagnosis of n-irAEs, a detailed characterization of neuroradiological features of ICI-induced neurotoxicities remains limited. In this Review, we provide a comprehensive description of the imaging findings associated with n-irAEs and summarize the diagnostic work-up of these challenging disorders, emphasizing the central role of neuroimaging in their evaluation.

Suppressor of cytokine signalling 3 (SOCS3), a protein that inhibits inflammatory molecules in microglia. A plant-derived phenolic compound, Syringic acid (SA), selectively increased SOCS3 levels in N-9 mouse microglial cells in a dose- and time-dependent manner. Similar effects were also observed in mouse primary microglia and astrocytes. In Lipopolysaccharide (LPS)-stimulated N-9 cells, SOCS3 expression decreased, but after SA treatment (LPS + SA), both mRNA and protein levels of SOCS3 increased. At the same time, pro-inflammatory mediators such as Tumor Necrosis Factor alpha (TNFα), Interleukin-1 receptor, type I (IL1R1), Interleukin-1 beta (IL1β), and Inducible Nitric Oxide Synthase (iNOS) were suppressed, along with a reduction in intracellular Reactive Oxygen Species generation (ROS) in LPS + SA-treated N-9 cells. Additionally, the expression of phospho-CREB was enhanced in LPS + SA-treated N-9 cells compared to only LPS-stimulated cells. Following the SiRNA knockdown of cAMP response element-binding protein (CREB), the upregulation of SOCS3 by syringic acid was abolished. These results confirm the role of CREB in this process. The findings suggest that SA promotes CREB activation, leading to SOCS3 expression, which may have therapeutic potential in neuroinflammatory disorders.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder identified by cognitive decline, memory loss, and behavioral changes, affecting approximately 50 million people worldwide. Genetic predisposition, environmental variables, and aging all play a role in the development of AD. Current therapeutic approaches primarily focus on alleviating symptoms through drugs such as donepezil and memantine. However, these treatments offer limited efficacy and may be accompanied by adverse effects. In contrast, natural therapies derived from algae present a promising alternative. Microalgae, including Chlorella and Spirulina, and macroalgae such as Fucus vesiculosus, Ecklonia cava, Sargassum, Laminaria japonica, and Fucus species, are rich in bioactive molecules having antioxidant and anti-inflammatory characteristics. These substances demonstrated potential in addressing the pathological features of AD, such as oxidative stress and neuroinflammation. Furthermore, advances in biotechnological tools like CRISPR-Cas9 gene editing are poised to enhance the efficacy of these natural therapies by targeting and modifying disease-associated genes. This review aims to bridge the fields of neurobiotechnology and marine bioresources by examining the synergistic potential of algal compounds and gene-editing strategies in combating Alzheimer's disease. Algal-derived compounds are utilized in pharmaceuticals, nutraceuticals, and dietary supplements, and may offer neuroprotective benefits that could aid in the prevention or treatment of AD.By integrating insights from molecular biology, pharmacology, and genomics, we seek to illuminate a novel, multidisciplinary framework for future therapeutic innovation.

Spinal cord injury (SCI) occurs either after a sudden trauma or through a chronic process at segmental levels of the spinal cord, leading to potentially deleterious neural consequences for the central nervous system (CNS) due to the death of neurons, oligodendrocytes, and astrocytes, as well as significant losses in motor, sensory, and autonomic functions. After SCI, an inflammatory response occurs, with cells such as macrophages and microglia being recruited. These cells are responsible for removing damaged tissue and secreting pro-inflammatory and anti-inflammatory cytokines and chemokines. Additionally, a protein called galectin-3 has been described as participating in cell activation, proliferation, and migration, acting as a mediator of inflammation in neurodegeneration. Thus, different populations of inflammatory cells in the injured nervous parenchyma can be characterized. In this study, we used a spinal cord contusion-compression model in wild-type C57Bl/6 mice (WT) and galectin-3 knockout mice (GAL3-/-) to histologically characterize the lesion, focusing on astrocyte, macrophage, and microglial populations. Our results showed a significant reduction in lesion propagation in GAL3-/- animals compared to WT animals. Moreover, GAL3-/- animals exhibited reduced astrogliosis compared to WT animals. Immunohistochemistry revealed that GAL3-/- animals had a larger area marked for the anti-inflammatory marker Arginase-1 and a smaller area marked for the pro-inflammatory marker iNOS compared to WT animals. We conclude that galectin-3 plays a critical role in the inflammatory process following spinal cord injury, and its absence may contribute to reduced lesion progression, decreased astrogliosis, and the promotion of an inflammatory response with a more anti-inflammatory profile. SIGNIFICANCE STATEMENT: This study highlights galectin-3 as a central mediator of the inflammatory response after spinal cord injury, demonstrating that galectin-3 deficiency limits lesion progression, attenuates astrogliosis, and promotes an anti-inflammatory profile. Thus, galectin-3 may represent a promising potential therapeutic target for clinical applications in neurodegenerative diseases.

According to the 2025 IPND consensus, live cell-based assays (live CBA) are now established as the reference standard for screening AQP4-IgG autoantibodies in patients suspected of having AQP4-IgG-positive Neuromyelitis optica spectrum (NMOSD). However, resource-limited settings in Latin America (LATAM), where even commercial kits (fixed CBA) can be scarce, face significant difficulties in accessing local live CBA due to its higher implementation cost, the time required for experimentation, and its technical complexity. In this narrative review, we identified 85 published studies that provide evidence of CBA locally used in LATAM countries. We identified 18 studies (21.1%) that used "live CBA" as the exclusive AQP4-IgG testing method. Brazil was the only country that had participated in all these reports. Argentina (n = 2, 2.3%), Mexico (n = 1, 1.1%), and Colombia (n = 1, 1.1%) have participated in studies combining "live CBA and fixed CBA". Our literature review suggests that live CBA availability is approximately 20% when considered as a single testing method, or up to 27.1% (n = 23) when used to varying degrees in conjunction with fixed CBA. Notably, several studies (n = 37, 43.5%) we analyzed relied solely on commercial fixed assays for AQP4-IgG testing. Worryingly, nearly one-third (n = 25, 29.4%) of the studies we analyzed still use commercial kits in combination with other non‑gold-standard methods to detect AQP4-IgG. In general, fixed CBA was the most sensitive method in 62 studies (72.9%) from LATAM. Based on our findings, here, we critically discuss the pressing need for live CBA dissemination across LATAM countries. This initiative will lead to more accurate epidemiological data, enable faster diagnosis, and improve access to highly effective therapies for AQP4-IgG-positive NMOSD patients living in this part of the world.

Serum glial fibrillary acidic protein (sGFAP) is increasingly studied as a biomarker of astroglial injury, but comparative data between ultra-sensitive analytical platforms are limited. This study evaluated the agreement between the newly developed VEUS technology and the established single-molecule array (SIMOA) method.

Evidence indicates that C-Chemokine Receptor 7 (CCR7) is implicated in behavioral dysfunction and that chlorogenic acid (CGA) exerts beneficial effects on cognitive deficits. However, the precise mechanisms by which CCR7 regulates cognitive dysfunction and whether CGA exerts its therapeutic effects through modulation of CCR7 signaling remain to be elucidated. Here, we investigated the specific role and mechanism of CCR7 on LPS-induced cognitive deficits using wild type (WT) and CCR7 knockout (CCR7) mice, and assessed the protective effect of CGA against these deficits. We found intracerebroventricular (i.c.v.) injection of LPS in WT mice induced learning and behavioral deficits in the open field test and Morris water maze (MWM) task, which were ameliorated in LPS-treated CCR7 mice. Furthermore, we observed increased expression of the anti-apoptotic marker Bcl-2 and synaptic markers (PSD95, SYN) in the hippocampus of LPS-treated CCR7 mice compared to that in LPS-stimulated WT mice. One potential mechanism of this action was attributed to the inhibition of LPS-induced, CCR7-mediated astrocyte activation, which was accompanied by reduced activation of its downstream proinflammatory signaling pathways (NF-κB, p38 and JNK) and the decreased production of pro-inflammatory factors including COX-2, iNOS, TNF-α, IL-1β and IL-6 in the hippocampus of LPS-treated CCR7 mice. Importantly, we demonstrated CGA ameliorated LPS-induced cognitive dysfunction, at least in part, through inhibition of CCR7-mediated astrocyte activation and its downstream NF-κB, p38 and JNK pathway activation. Collectively, precise elucidation of the inhibitory effect of CGA on CCR7 signaling in LPS-stimulated mice contributes to the development of strategies for controlling neuroinflammation-mediated cognitive disorders.

Multiple Sclerosis (MS) is an autoimmune, demyelinating, inflammatory disorder. The anti-CD20 monoclonal antibody ocrelizumab targets B cells, effectively controlling the disease. MicroRNAs (miRNAs), small molecules modulating immune responses and neuroinflammation, may serve as biomarkers for disease progression, though the impact of anti-CD20 remains unclear. We hereby selected three miRNAs of interest for their relevance in experimental autoimmune encephalomyelitis (EAE) and MS, miR-124a-3p, miR-125b-5p, and miR-223-3p.

Drugs able to efficiently counteract primary progressive MS (PP-MS) remain an unmet need. The availability of reliable animal models of PP-MS might boost the identification of treatments capable of counteracting disease evolution. Recently, we characterized primary progressive EAE (PP-EAE) in NOD/ShiLtJ mice, showing that it recapitulates several key features of PPMS. However, a fundamental difference between PPMS and PPEAE is that the latter is triggered by loss of tolerance deliberately induced via peripheral expansion of myelin-specific effector T cells (Teff). In the present study, we report that NOD/ShiLtJ mice challenged with complete Freund's adjuvant (CFA) to prevent diabetes onset, developed spontaneous PP-EAE (SPP-EAE). Specifically, we report that the sole CFA challenge induced encephalomyelitis with a similar pattern of that prompted by the complete immunization protocol including CFA, pertussis toxin and MOG. Mice with SPP-EAE show primary progressive disease evolution, widespread neurodegeneration, and insensitivity to dexamethasone-dependent immunosuppression. Remarkably, however, at variance with the rapid onset of PP-EAE, SPP-EAE manifested after a latency of approximately 4.5 months following CFA injection. This model may represent a valuable experimental tool to study mechanisms underlying spontaneous loss of self-tolerance toward CNS antigens and MS progression, as well as to identify therapies of relevance to treatment of PMS patients.

Myasthenia gravis (MG) is a signaling disorder caused by immune abnormalities at the neuromuscular junction, resulting in symptoms such as muscle weakness and fatigue. Groundbreaking research since the 1970s has revealed the pathophysiology of this disease to be a T cell-dependent, B cell-associated antibody-producing disease. Half a century ago, many patients died of the disease, Today, the mortality rate has declined with many patients achieving remission. Here, I review MG pathophysiology, issues in treatment considerations specific to childhood and adolescence, and examine how racial, cultural, and geographic differences impact the clinical phenotype and treatment practices in childhood-onset MG across East Asia and Western Europe.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by unusual social interactions, limited speech, and repetitive behaviors or hobbies. The BTBR T Itpr3J (BTBR) inbred mice are commonly used as a model for ASD because they display many genetic traits associated with autism. Ursolic acid, a naturally occurring compound found in several plants, has shown promise as a treatment for various inflammatory disorders and related experimental models. This study aimed to explore the potential effects of ursolic acid on self-grooming, marble burying, and social behaviors in BTBR mice. We examined how ursolic acid affects the expression of Th1 (IFN-γ, TNF-α, STAT1, STAT4, and T-bet), Th17 (IL-17, RORγt, and STAT3), and T regulatory (Treg; IL-10, TGF-β1, and Foxp3) markers in CD4 T cells within the spleens of BTBR and C57BL/6 mice. Additionally, we assessed the impact of ursolic acid on brain mRNA levels of IFN-γ, TNF-α, STAT1, STAT4, T-bet, IL-17, RORγ, STAT3, IL-10, TGF-β1, and Foxp3. Treatment with ursolic acid significantly affected behavioral issues in BTBR mice. In these animals, ursolic acid reduced the levels of Th1 and Th17 cells while increasing the levels of Treg cells. Furthermore, it decreased the expression of Th1 and Th17 mRNA and increased the expression of Treg-related mRNA in the brain. Our findings suggest that, due to its anti-inflammatory properties, ursolic acid may be a beneficial treatment for behavioral impairments in BTBR mice.

Autoimmune encephalitis (AE) comprises a group of immune-mediated central nervous system disorders and can present with psychiatric symptoms. This study aimed to prospectively identify and characterize the AE group in first psychotic episode (FEP) at the tertiary psychiatric hospital using clinical and instrumental data in combination with modified algorithm for AE in FEP; and retrospectively evaluate current diagnostic algorithms for AE and autoimmune psychosis (AP) based on obtained empirical data.

This study investigates the shared molecular mechanisms between major depressive disorder (MDD) and systemic lupus erythematosus (SLE) through integrated bioinformatics analysis. Analysis of multiple GEO datasets identified 23 common differentially expressed genes (coDEGs), primarily enriched in immune and metabolic pathways. Among 13 high-confidence hub genes derived from protein-protein interaction networks, two biomarkers-KLRB1 and RETN-were consistently selected by machine learning algorithms (including LASSO, SVM, and Random Forest) and validated across independent cohorts. Both biomarkers demonstrated high diagnostic accuracy, with combined AUC values of 0.929 for MDD and 0.948 for SLE. Immune infiltration analysis revealed common reductions in NK cells and elevated monocyte levels in both disorders. KLRB1 expression was positively correlated with NK cell function, while RETN showed disease-specific immune correlations. Gene Set Enrichment Analysis (GSEA) indicated associations between both genes and neurodegeneration-related pathways. Additionally, a predicted ceRNA network suggested potential upstream non-coding RNA regulators. These results underscore dysregulated innate immunity and inflammatory pathways as key common features of MDD and SLE, providing new insights into their diagnosis and therapeutic targeting.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Physiological monitoring may be useful for monitoring the progression of MS and its underlying neurodegenerative processes OBJECTIVE: This cross-sectional study evaluated the feasibility of assessing associations of physiological parameters measured by a wearable sensor with CNS atrophy and lesion burden in individuals with MS.

Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by neuromuscular impairment. While its motor symptoms are well-documented, its neuropsychological impact remains underexplored. This multicenter retrospective case-control study explores the prevalence of psychopathology in MG patients compared to healthy controls (HCs), analyzing correlations between disease severity and psychiatric disorders.

Emerging evidence suggests that imbalanced T-cell activity and immune dysfunction may contribute to migraine pathogenesis. However, the specific immune pathways remain unclear, particularly the role of B cells. To explore B-cell-related mechanisms, this study focused on two key members of the tumor necrosis factor (TNF) family, namely B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL), which play critical roles in B-cell survival and regulation. This study examined BAFF and APRIL expression in peripheral blood samples from migraine patients during pre-ictal, ictal, and post-ictal phases (n = 9) and in healthy controls (n = 9). BAFF levels increased during the ictal phase (p = 0.011) and declined in the post-ictal phase, whereas APRIL remained consistently downregulated relative to controls. The divergent patterns of BAFF and APRIL reveal a novel B-cell-related immune signature that may contribute to migraine pathogenesis. These preliminary findings support further studies to confirm these patterns and investigate the functional role of the BAFF-APRIL pathway in migraine.