ArticleNeurology(R) neuroimmunology & neuroinflammation2021
New BBB Model Reveals That IL-6 Blockade Suppressed the BBB Disorder, Preventing Onset of NMOSD.
Article in Neurology(R) neuroimmunology & neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 91 citations in OpenAlex.
- Serum neurofilament light chain levels at attack predict post-attack disability worsening and are mitigated by inebilizumab: analysis of four potential biomarkers in neuromyelitis optica spectrum disorder.Journal of neurology, neurosurgery, and psychiatry · 2023Trial
- Posterior reversible encephalopathy syndrome associated with anti-N-methyl-ᴅ-aspartate receptor encephalitis: a case report.Encephalitis (Seoul, Korea) · 2026Article
- Neutrophil extracellular traps exacerbate blood-brain barrier disruption in neuromyelitis optica spectrum disorder.Journal of neuroinflammation · 2026Article
- Blood IL-6 is a critical trigger of depressive symptoms in a mouse model for human atopic dermatitis.Translational psychiatry · 2026Article
- TRIM21 autoantibodies are associated with blood-brain barrier dysfunction in a subgroup of neuromyelitis optica spectrum disorder.Acta neuropathologica communications · 2026Article
- Sigma-1 receptor regulates HIV-1 and methamphetamine-induced endothelial/pericyte barrier impairment via strain-specific inflammatory responses and mitochondrial dysregulation.Journal of neuroinflammation · 2026Article
- Modulation of Cytokines and Immune Cells by Plasma Exchange in Patients With Certain Autoimmune Neurological Diseases.Immunity, inflammation and disease · 2026Article
- Anti-IL-6 Receptor Antibody Suppresses Visual Dysfunction in AQP4 Peptide-Immunized Mice.Translational vision science & technology · 2026Article
- The role of CSF IL-6 levels in diagnosis and outcome prediction of autoimmune encephalitis.Frontiers in immunology · 2026Article
- Case Report: Rare co-occurrence of NMOSD and capillary leak syndrome treated with satralizumab.Frontiers in immunology · 2026Review
- Comparison of clinical and laboratory characteristics of neuromyelitis optica spectrum disorder with or without anti-connective tissue antibodies: an 18-month cohort follow-up.Frontiers in immunology · 2026Article
- Serum interleukin-6 as a neuroinflammatory biomarker across the spectrum of neurological disorders: a large-scale retrospective cohort study of 6,465 individuals.Frontiers in immunology · 2026Observational
- Dissecting NMOSD pathogenesis through animal models: a mechanism-oriented systems perspective.Frontiers in immunology · 2026Review
- Differentiation of acute-phase AQP4-IgG+ optic neuritis from CNS inflammatory diseases using optic nerve head blood flow analysis.Scientific reports · 2025Article
- Aquaporin-4 Peptide Injection in Mice Induces Retinal and Optic Nerve Alterations That Simulate Those of Neuromyelitis Optica Spectrum Disorder.Translational vision science & technology · 2025Article
- Article
- Breaking the Barrier: The Role of Proinflammatory Cytokines in BBB Dysfunction.International journal of molecular sciences · 2025Review
- Clinical and pathological risk factors for postencephalitic epilepsy after herpes simplex virus-1 encephalitis in children.Scientific reports · 2025Article
- Differentiating optic neuropathies using laser speckle flowgraphy: Evaluating blood flow patterns in the optic nerve head and peripapillary choroid.Acta ophthalmologica · 2025Article
- Clinical characteristics and factors associated with recurrence and long-term prognosis in patients with MOGAD.Frontiers in immunology · 2025Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesTo evaluate the pathophysiology of neuromyelitis optica spectrum disorder (NMOSD) and the therapeutic mechanism and levels of interleukin-6 (IL-6) blockade (satralizumab), especially with respect to blood-brain barrier (BBB) disruption with the new in vitro and ex vivo human BBB models and in vivo model.
methodsWe constructed new static in vitro and flow-based ex vivo models for evaluating continued barrier function, leukocyte transmigration, and intracerebral transferability of neuromyelitis optica-immunoglobulin G (NMO-IgG) and satralizumab across the BBB using the newly established triple coculture system that are specialized to closely mimic endothelial cell contact of pericytes and endfeet of astrocytes. In the in vivo study, we assessed the effects of an anti-IL-6 receptor antibody for mice (MR16-1) on in vivo BBB disruption in mice with experimental autoimmune encephalomyelitis in which IL-6 concentration in the spinal cord dramatically increases.
resultsIn vitro and ex vivo experiments demonstrated that NMO-IgG increased intracerebral transferability of satralizumab and NMO-IgG and that satralizumab suppressed the NMO-IgG-induced transmigration of T cells and barrier dysfunction. In the in vivo study, the blockade of IL-6 signaling suppressed the migration of T cells into the spinal cord and prevented the increased BBB permeability. DISCUSSION: These results suggest that (1) our triple-cultured in vitro and in ex vivo BBB models are ideal for evaluating barrier function, leukocyte transmigration, and intracerebral transferability; (2) NMO-IgG increased the intracerebral transferability of NMO-IgG via decreasing barrier function and induced secretion of IL-6 from astrocytes causing more dysfunction of the barrier and disrupting controlled cellular infiltration; and (3) satralizumab, which can pass through the BBB in the presence of NMO-IgG, suppresses the BBB dysfunction and the infiltration of inflammatory cells, leading to prevention of onset of NMOSD.
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Registered trials
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