ArticleThe American journal of pathology1998
Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy.
Article in The American journal of pathology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 317 citations in OpenAlex.
- Pooled it
- Selective inhibition of TLR2 stimulates the maturation of oligodendroglial progenitor cells to oligodendrocytes.NeuroImmune pharmacology and therapeutics · 2026Article
- Enhanced myelination potential of human mature oligodendrocytes by TNF and IFNG combination.Journal of neuroinflammation · 2026Article
- Pro-Inflammatory Molecules Implicated in Multiple Sclerosis Divert the Development of Human Oligodendrocyte Lineage Cells.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- Targeting cytokine networks in neuroinflammatory diseases.Nature reviews. Drug discovery · 2024Review
- The contribution of tumor necrosis factor to multiple sclerosis: a possible role in progression independent of relapse?Journal of neuroinflammation · 2024Review
- An Overview of Multiple Sclerosis In Vitro Models.International journal of molecular sciences · 2024Review
- Muscle-building supplement β-hydroxy β-methylbutyrate stimulates the maturation of oligodendroglial progenitor cells to oligodendrocytes.Journal of neurochemistry · 2024Article
- Discovery of a brain penetrant small molecule antagonist targeting LPA1 receptors to reduce neuroinflammation and promote remyelination in multiple sclerosis.Scientific reports · 2024Article
- Myelin Pathology in Alzheimer's Disease: Potential Therapeutic Opportunities.Aging and disease · 2024Review
- Article
- An Animal Model for Chronic Meningeal Inflammation and Inflammatory Demyelination of the Cerebral Cortex.International journal of molecular sciences · 2023Article
- Effect of chronic intermittent ethanol vapor exposure on RNA content of brain-derived extracellular vesicles.Alcohol (Fayetteville, N.Y.) · 2022Article
- The Possible Role of Neural Cell Apoptosis in Multiple Sclerosis.International journal of molecular sciences · 2022Review
- Article
- Structural Plasticity of the Hippocampus in Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- The role of inflammasomes in vascular cognitive impairment.Molecular neurodegeneration · 2022Review
- Citrullinated myelin induces microglial TNFα and inhibits endogenous repair in the cuprizone model of demyelination.Journal of neuroinflammation · 2021Article
- Exploring the roles of tryptophan metabolism in MS beyond neuroinflammation and neurodegeneration: A paradigm shift to neuropsychiatric symptoms.Brain, behavior, & immunity - health · 2021Review
- Review
52 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The scientific dogma that multiple sclerosis (MS) is a disease caused by a single pathogenic mechanism has been challenged recently by the heterogeneity observed in MS lesions and the realization that not all patterns of demyelination can be modeled by autoimmune-triggered mechanisms. To evaluate the contribution of local tumor necrosis factor (TNF) ligand/receptor signaling pathways to MS immunopathogenesis we have analyzed disease pathology in central nervous system-expressing TNF transgenic mice, with or without p55 or p75TNF receptors, using combined in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling and cell identification techniques. We demonstrate that local production of TNF by central nervous system glia potently and selectively induces oligodendrocyte apoptosis and myelin vacuolation in the context of an intact blood-brain barrier and absence of immune cell infiltration into the central nervous system parenchyma. Interestingly, primary demyelination then develops in a classical manner in the presence of large numbers of recruited phagocytic macrophages, possibly the result of concomitant pro-inflammatory effects of TNF in the central nervous system, and lesions progress into acute or chronic MS-type plaques with axonal damage, focal blood-brain barrier disruption, and considerable oligodendrocyte loss. Both the cytotoxic and inflammatory effects of TNF were abrogated in mice genetically deficient for the p55TNF receptor demonstrating a dominant role for p55TNF receptor-signaling pathways in TNF-mediated pathology. These results demonstrate that aberrant local TNF/p55TNF receptor signaling in the central nervous system can have a potentially major role in the aetiopathogenesis of MS demyelination, particularly in MS subtypes in which oligodendrocyte death is a primary pathological feature, and provide new models for studying the basic mechanisms underlying oligodendrocyte and myelin loss.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.