ArticleActa neuropathologica communications2020
Persistent elevation of intrathecal pro-inflammatory cytokines leads to multiple sclerosis-like cortical demyelination and neurodegeneration.
Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 74 citations in OpenAlex.
- NAA is a Marker of Disability in Secondary-Progressive MS: A Proton MR Spectroscopic Imaging Study.AJNR. American journal of neuroradiology · 2020Trial
- Article
- Molecular Mimicry Between Epstein-Barr Virus and Human Herpesvirus-6 Proteins and Central Nervous System Proteins: Implications for T and B Cell Immunogenicity in an In Silico Study.Immunity, inflammation and disease · 2026Article
- Mechano responsiveness of neuroimmune cross-talk in bone and joints: A narrative review with implications for force-based manipulations.Musculoskeletal science & practice · 2026Review
- The effect of cladribine tablets on intrathecal inflammation in relapsing-remitting multiple sclerosis.Journal of neuroinflammation · 2026Article
- Dysregulation of the endosomal sorting complex III is linked to neurodegeneration in progressive multiple sclerosis.Brain pathology (Zurich, Switzerland) · 2026Article
- Smoldering neuroinflammation in progressive multiple sclerosis: mechanisms, imaging biomarkers, and therapeutic opportunities.Frontiers in immunology · 2026Review
- MLKL Modulates Necroptosis and Neuroinflammation in a Mouse Model of MS.Inflammation · 2025Article
- Spatiotemporal subtypes of brain and spinal cord atrophy in neuromyelitis optica spectrum disorders and multiple sclerosis.BMC medicine · 2025Article
- Brain macrophages and pial fibroblasts promote inflammation in a hypomyelination model.Acta neuropathologica communications · 2025Article
- Neuropathological and cerebrospinal fluid correlates of choroid plexus inflammation in progressive multiple sclerosis.Brain pathology (Zurich, Switzerland) · 2025Article
- Intrathecal Inflammatory Profile and Gray Matter Damage Predict Progression Independent of Relapse Activity in Early Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- From RIPK1 to Necroptosis: Pathogenic Mechanisms in Neurodegenerative Diseases.Neurochemical research · 2025Review
- Thalamic atrophy in multiple sclerosis is associated with tract disconnection and altered microglia.Acta neuropathologica · 2025Article
- Laser-Induced Cortical Lesions in Mice as a Model for Progressive Multiple Sclerosis Pathology.Biomedicines · 2025Article
- The Possible Role of Metformin and Fibroblast Growth Factor-21 in Multiple Sclerosis Neuropathology: Birds of a Feather Flock Together.The European journal of neuroscience · 2025Review
- Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond.International journal of molecular sciences · 2024Review
- Article
- The Hidden Hand in White Matter: Pericytes and the Puzzle of Demyelination.ACS pharmacology & translational science · 2024Review
- The contribution of tumor necrosis factor to multiple sclerosis: a possible role in progression independent of relapse?Journal of neuroinflammation · 2024Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Analysis of isolated meninges and cerebrospinal fluid (CSF) of post-mortem MS cases has shown increased gene and protein expression for the pro-inflammatory cytokines: tumour necrosis factor (TNF) and interferon-γ (IFNγ). Here we tested the hypothesis that persistent production of these cytokines in the meningeal compartment and diffusion into underlying GM can drive chronic MS-like GM pathology. Lentiviral transfer vectors were injected into the sagittal sulcus of DA rats to deliver continuous expression of TNF + IFNγ transgenes in the meninges and the resulting neuropathology analysed after 1 and 2 months. Injection of TNF + IFNγ viral vectors, with or without prior MOG immunisation, induced extensive immune cell infiltration (CD4+ and CD8+ T-cells, CD79a + B-cells and macrophages) in the meninges by 28 dpi, which remained at 2 months. Control GFP viral vector did not induce infiltration. Subpial demyelination was seen underlying these infiltrates, which was partly dependant on prior myelin oligodendrocyte glycoprotein (MOG) immunisation. A significant decrease in neuronal numbers was seen at 28 and 56 days in cortical layers II-V that was independent of MOG immunisation. RNA analysis at 28 dpi showed an increase in expression of necroptotic pathway genes, including RIP3, MLKL, cIAP2 and Nox2. PhosphoRIP3+ and phosphoMLKL+ neurons were present in TNF + IFNγ vector injected animals, indicating activation of necroptosis. Our results suggest that persistent expression of TNF in the presence of IFNγ is a potent inducer of meningeal inflammation and can activate TNF signalling pathways in cortical cells leading to neuronal death and subpial demyelination and thus may contribute to clinical progression in MS.
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