ArticleNature neuroscience2013
M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination.
Article in Nature neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04925349 (MATRIX - "Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy, Metachromatic Leukodystrophy and Adult Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia"), which is not on this map. Cited by 984 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
MATRIX - "Modeling Macrophages Activation Pattern in X-linked Adrenoleukodystrophy, Metachromatic Leukodystrophy and Adult Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia"
Who cites it
984 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Recent Advances in Interventions Targeting Remyelination and a Systematic Review of Remyelinating Effects of Approved Disease-Modifying Treatments for Multiple Sclerosis.European journal of neurology · 2025Pooled it
- Role and Mechanism of Microglia in White Matter Injury Recovery in Ischemic Stroke.Immunity, inflammation and disease · 2025Pooled it
- Complementary PET and MRI of myeloperoxidase activity as a noninvasive surrogate for tissue acrolein in experimental neuroinflammation.NeuroImage · 2026Article
- Neuro-immune interactions in tumors, immune-related disorders, and infections.Signal transduction and targeted therapy · 2026Review
- Rethinking the Oligodendrocyte Progenitor Cell: One Cell, Many Functions.The European journal of neuroscience · 2026Review
- Review
- M2-associated microglial states in oligodendrocyte regulation and white matter repair in vascular dementia.Journal of translational medicine · 2026Review
- Integrated analysis of single-cell transcriptome identifies a glial-neurovascular signaling trajectory in brain repair after ischemia.Biology direct · 2026Article
- Beyond the Wiring: White Matter as a Dynamic Regulator of Brain Function and Disease.Neuroscience bulletin · 2026Review
- The Neurovascular Niche: A Gathering Venue for Neuroinflammation and Remyelination in Multiple Sclerosis.Acta physiologica (Oxford, England) · 2026Review
- Review
- The Neuroimmune Duality of CD4⁺ T Cells: Drivers of Damage and Repair in the Brain.Molecular neurobiology · 2026Review
- A Lactate-H4K12la-HDAC1 epigenetic axis governs microglial state transitions during experimental autoimmune encephalomyelitis in female mice.Nature communications · 2026Article
- Pro-repair properties of a human embryonic stem cell-derived astrocyte cell therapy in demyelinating disorders.Stem cell reports · 2026Article
- CSF1R inhibition following antibody mediated demyelination has limited impact on remyelination.Acta neuropathologica communications · 2026Article
- Spatial mapping and senolytic targeting of senescent and disease-associated microglia in aged mouse brain white matter.Nature aging · 2026Article
- Near‑Infrared Photobiomodulation in White‑Matter Disease: From Microglial States to Measurable Endpoints.Neuromolecular medicine · 2026Review
- Oligodendroglia as Active Immunomodulators in Demyelinating Diseases.Neuroscience bulletin · 2026Review
- Myelin Repair as a Neuroprotective Strategy for Multiple Sclerosis: From Bench to Bedside.Medicina (Kaunas, Lithuania) · 2026Review
- Review
924 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
The lack of therapies for progressive multiple sclerosis highlights the need to understand the regenerative process of remyelination that can follow CNS demyelination. This involves an innate immune response consisting of microglia and macrophages, which can be polarized to distinct functional phenotypes: pro-inflammatory (M1) and anti-inflammatory or immunoregulatory (M2). We found that a switch from an M1- to an M2-dominant response occurred in microglia and peripherally derived macrophages as remyelination started. Oligodendrocyte differentiation was enhanced in vitro with M2 cell conditioned media and impaired in vivo following intra-lesional M2 cell depletion. M2 cell densities were increased in lesions of aged mice in which remyelination was enhanced by parabiotic coupling to a younger mouse and in multiple sclerosis lesions that normally show remyelination. Blocking M2 cell-derived activin-A inhibited oligodendrocyte differentiation during remyelination in cerebellar slice cultures. Thus, our results indicate that M2 cell polarization is essential for efficient remyelination and identify activin-A as a therapeutic target for CNS regeneration.
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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 Socratic graph.