ArticleAnnals of neurology2013
Iron and neurodegeneration in the multiple sclerosis brain.
Article in Annals of neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05961644 (Safety and Efficacy of Subcutaneous Cladribine for Nonrelapsing, Secondary Progressive Multiple Sclerosis), which is not on this map. Cited by 280 papers, 4 of them syntheses that pooled it.
What it found
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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.
Safety and Efficacy of Subcutaneous Cladribine for Nonrelapsing, Secondary Progressive Multiple Sclerosis (CLASP-MS): a Randomized, Placebo-controlled, Double-blind, Phase 2 Study.
Who cites it
280 citing papers in PubMed, 4 syntheses or guidelines pooled it, 516 citations in OpenAlex.
- Iron accumulation in multiple sclerosis and implications for cognitive and clinical progression: a systematic review of advanced neuroimaging studies.Journal of neurology · 2026Pooled it
- Associations between chronic active lesions and clinical outcomes in multiple sclerosis: A systematic literature review.Journal of managed care & specialty pharmacy · 2025Pooled it
- Quantitative susceptibility mapping in multiple sclerosis: A systematic review and meta-analysis.NeuroImage. Clinical · 2024Pooled it
- Can MRI measure myelin? Systematic review, qualitative assessment, and meta-analysis of studies validating microstructural imaging with myelin histology.NeuroImage · 2021Pooled it
- Brain oxygen extraction fraction mapping in patients with multiple sclerosis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Trial
- Predicting disability progression and cognitive worsening in multiple sclerosis using patterns of grey matter volumes.Journal of neurology, neurosurgery, and psychiatry · 2021Trial
- The SLC7A11 Thermostat: A Molecular Signaling Switch Between Ferroptosis and Disulfidptosis in Neurodegenerative Disease.Molecular neurobiology · 2026Review
- Article
- Beyond Relapses: A Multimodal Biomarker Framework for Progression Independent of Relapse Activity and Smouldering Multiple Sclerosis.Brain sciences · 2026Review
- Grey matter degeneration during multiple sclerosis is linked to activation of neuronal necroptosis by oxidized phosphatidylcholines.Research square · 2026Article
- Monocyte infiltration induces CNS arginine catabolism to fuel neuroinflammation.Nature immunology · 2026Article
- Tract-based χ-separation imaging differentiates multiple sclerosis from neuromyelitis optica spectrum disorder by mapping iron and myelin signatures.BMC medical imaging · 2026Article
- How does iron cross the abluminal membrane of the blood-brain barrier.Experimental & molecular medicine · 2026Review
- Exploring and Targeting the Connection of Iron and Copper Homeostasis to Neurodegenerative Diseases.MedComm · 2026Review
- The hypoxia-inflammation cycle as a key mechanism of smoldering inflammation and progression in multiple sclerosis.Acta neuropathologica · 2026Review
- Erythrocyte Fragility in Progressive Multiple Sclerosis.European journal of neurology · 2026Article
- Spatial gene expression and functional network abnormalities in multiple sclerosis: exploring biological influence on brain functional reorganization.Translational psychiatry · 2026Article
- Iron-Rim Lesions in the Optic Chiasm in Multiple Sclerosis: A Neuropathologic Case Series.Neurology · 2026Article
- Voxel-Wise Whole-Brain Analysis in Quantitative Susceptibility Mapping: A Narrative Review.Human brain mapping · 2026Review
- Oxidized phosphatidylcholines deposition drives chronic neurodegeneration in a mouse model of progressive multiple sclerosis via IL-1β signaling.Nature neuroscience · 2026Article
220 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
6 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveIron may contribute to the pathogenesis and progression of multiple sclerosis (MS) due to its accumulation in the human brain with age. Our study focused on nonheme iron distribution and the expression of the iron-related proteins ferritin, hephaestin, and ceruloplasmin in relation to oxidative damage in the brain tissue of 33 MS and 30 control cases.
methodsWe performed (1) whole-genome microarrays including 4 MS and 3 control cases to analyze the expression of iron-related genes, (2) nonheme iron histochemistry, (3) immunohistochemistry for proteins of iron metabolism, and (4) quantitative analysis by digital densitometry and cell counting in regions representing different stages of lesion maturation.
resultsWe found an age-related increase of iron in the white matter of controls as well as in patients with short disease duration. In chronic MS, however, there was a significant decrease of iron in the normal-appearing white matter (NAWM) corresponding with disease duration, when corrected for age. This decrease of iron in oligodendrocytes and myelin was associated with an upregulation of iron-exporting ferroxidases. In active MS lesions, iron was apparently released from dying oligodendrocytes, resulting in extracellular accumulation of iron and uptake into microglia and macrophages. Iron-containing microglia showed signs of cell degeneration. At lesion edges and within centers of lesions, iron accumulated in astrocytes and axons.
interpretationIron decreases in the NAWM of MS patients with increasing disease duration. Cellular degeneration in MS lesions leads to waves of iron liberation, which may propagate neurodegeneration together with inflammatory oxidative burst.
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What OpenQuestion holds
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.