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Cited by 16Multiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanismsMesenchymal stem cell research

BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis

Open access
Bergner, Caroline Gertrud, van der Meer, Franziska, Franz, Jonas, Vakrakou, Aigli, Würfel, Thea, Nessler, Stefan, Schäfer, Lisa, Nau-Gietz, Cora +13 more·2025·Brain
DOI 10.1093/brain/awae293PMC PMC11884765
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Abstract

Remyelination is a crucial regenerative process in demyelinating diseases, limiting persisting damage to the CNS. It restores saltatory nerve conduction and ensures trophic support of axons. In patients with multiple sclerosis, remyelination has been observed in both white and grey matter and found to be more efficient in the cortex. Brain-enriched myelin-associated protein 1 (BCAS1) identifies oligodendrocyte lineage cells in the stage of active myelin formation in development and regeneration. Other than in the white matter, BCAS1+ oligodendrocytes are maintained at high densities in the cortex throughout life. Here, we investigated cortical lesions in human biopsy and autopsy tissue from patients with multiple sclerosis in direct comparison to demyelinating mouse models and demonstrate that following a demyelinating insult BCAS1+ oligodendrocytes in remyelinating cortical lesions shift from a quiescent to an activated, internode-forming morphology co-expressing myelin-associated glycoprotein (MAG), necessary for axonal contact formation. Of note, activated BCAS1+ oligodendrocytes are found at early time points of experimental demyelination amidst ongoing inflammation. In human tissue, activated BCAS1+ oligodendrocytes correlate with the density of myeloid cells, further supporting their involvement in an immediate regenerative response. Furthermore, studying the microscopically normal appearing non demyelinated cortex in patients with chronic multiple sclerosis, we find a shift from quiescent BCAS1+ oligodendrocytes to mature, myelin-maintaining oligodendrocytes, suggesting oligodendrocyte differentiation and limited replenishment of BCAS1+ oligodendrocytes in long-standing disease. We also demonstrate that part of perineuronal satellite oligodendrocytes are BCAS1+ and contribute to remyelination in human and experimental cortical demyelination. In summary, our results provide evidence from human tissue and experimental models that BCAS1+ cells in the adult cortex represent a population of pre-differentiated oligodendrocytes that rapidly react after a demyelinating insult thus enabling immediate myelin regeneration. In addition, our data suggest that limited replenishment of BCAS1+ oligodendrocytes may contribute to the remyelination failure observed in the cortex in chronic multiple sclerosis.

AI snapshot

Written from the paper’s full text.

TL;DR

Cortical BCAS1+ oligodendrocytes are a pre-differentiated, partly perineuronal satellite population that rapidly shifts to an activated, internode-forming, MAG-expressing phenotype after demyelination in mouse models and human MS tissue. In chronic MS, normal-appearing cortex shows reduced BCAS1+ oligodendrocytes and increased mature TPPP/p25+ oligodendrocytes, suggesting limited replenishment may contribute to later remyelination failure.

Key findings

  • In mouse cortex, total BCAS1+ cell density did not change significantly during cuprizone treatment or after withdrawal, but activated/myelinating BCAS1+ oligodendrocytes increased early, peaking at 4 weeks of cuprizone when TPPP/p25+ oligodendrocyte loss was severe and ongoing.
  • In human MS biopsies, 15/24 cortical lesions showed early ongoing remyelination with abundant process-bearing BCAS1+ oligodendrocytes; total BCAS1+ cells were comparable to control/normal-appearing cortex in remyelinating lesions but severely reduced in demyelinated lesions.
  • BCAS1+ perineuronal satellite oligodendrocytes contributed to remyelination: about 37.4 ± 2.5% of BCAS1+ oligodendrocytes in control mouse cortex and 40.1 ± 4.8% in control human biopsy tissue were satellite cells; activated BCAS1+ satellite cells increased in early remyelinating MS lesions.
  • In chronic MS autopsy cortex, activated BCAS1+ oligodendrocytes were found in 26.1% of cortical lesions; normal-appearing cortex showed significantly reduced total BCAS1+ oligodendrocytes and increased TPPP/p25+ mature oligodendrocytes, while total Olig2+ lineage cells were unaltered.

Methods

  • Human tissue: formalin-fixed, paraffin-embedded archival biopsy and autopsy tissue; 24 MS biopsies and 26 MS autopsies, plus 11 control biopsies and 31 control autopsies. Lesions were classified as demyelinated, remyelinated, or normal-appearing cortex using (immuno-)histochemistry for myelin components.
  • Mouse models: cuprizone-induced cortical demyelination in 7- to 8-week-old male C57BL/6J mice fed 0.25% cuprizone for 1, 2, 3, 4, or 6 weeks and analyzed during treatment and at 2, 4, 6, and 21 days after withdrawal; focal cortical demyelination in Th/+ mice immunized with recombinant MOG1–125/CFA and stereotactically injected with TNFα/IFNγ.
  • Analysis: immunohistochemistry/immunofluorescence for BCAS1, MAG, TPPP/p25, Olig2, KiM1P, Mac3, MBP, NeuN; quantification of cell densities and morphology; statistics included Kolmogorov–Smirnov, t-test/Mann–Whitney, one-way/two-way ANOVA with post hoc tests, Kruskal–Wallis with Dunn’s test, and Spearman’s rho correlation.

Limitations

  • Stated: the authors report no robust correlations between BCAS1+ oligodendrocyte densities and age, sex, disease type, or disease duration in human biopsy or autopsy tissue, and state that larger sample sizes are required to determine these influences.
  • Stated: further experimental work, including lineage tracing and assessment of internode length and g-ratio, is needed to determine whether BCAS1 expression marks all pre-/actively myelinating oligodendrocytes and to directly associate newly formed internodes with BCAS1.
  • Evident: human findings are largely descriptive/correlational across archival biopsy and autopsy tissue, and the study does not establish causality for the proposed sequence from quiescent BCAS1+ cells to remyelination or for the link between BCAS1+ depletion and chronic remyelination failure.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/brain/awae293

Cites

69 of 69 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

48 of 74 cited sources checked · 24 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    BCAS1 identifies oligodendrocyte lineage cells in the stage of active myelin formation in development and regeneration.

    “Brain-enriched myelin-associated protein 1 (BCAS1) identifies oligodendrocyte lineage cells in the stage of active myelin formation in development and regeneration.”
    • Also stated in: § Introduction · boosted
      “We and others have recently shown that immunohistochemistry for brain-enriched myelin-associated protein 1 (BCAS1) identifies process-rich pre-myelinating and internode-forming actively myelinating oligodendrocytes in mouse and human tissue.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [29] Fard, 2017, BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions, Sci Transl Med source
    • cites [30] Ishimoto, 2017, Mice lacking BCAS1, a novel myelin-associated protein, display hypomyelination, schizophrenia-like abnormal behaviors, and upregulation of inflammatory genes in the brain, Glia source
    • cites [31] Kaji, 2020, BCAS1-positive immature oligodendrocytes are affected by the α-synuclein-induced pathology of multiple system atrophy, Acta Neuropathol Commun source
  • Premisecitation

    In the cortex, unlike white matter, BCAS1+ oligodendrocytes are maintained at high densities throughout life.

    “Other than in the white matter, BCAS1+ oligodendrocytes are maintained at high densities in the cortex throughout life.”
    • Also stated in: § Introduction · plain
      “In contrast, in the cerebral cortex, the population of BCAS1+ oligodendrocytes remains substantial throughout life and only slowly decreases with age.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [29] Fard, 2017, BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions, Sci Transl Med source
  • Interpretationcitation

    The reduction in all oligodendrocyte lineage cells in chronic demyelinated cortical lesions suggests an overall consumption of oligodendrocytes.

    “suggesting an overall consumption of oligodendrocytes, as reported previously.41”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [41] Rodriguez, 2014, Oligodendroglia in cortical multiple sclerosis lesions decrease with disease progression, but regenerate after repeated experimental demyelination, Acta Neuropathol source
    • Rests on an assumption: Olig2 immunostaining marks all cells of the oligodendrocyte lineage.
  • Interpretationreasoning

    In cortical grey matter, oligodendrocyte recruitment and remyelination is an early phenomenon in MS lesion formation that occurs in the immediate post-phagocytic phase when foam cells are still abundant in demyelinated lesions.

    “For cortical grey matter, this now indicates that oligodendrocyte recruitment and remyelination is an early phenomenon in MS lesion formation that occurs in the immediate post-phagocytic phase when foam cells are still abundant in the demyelinated lesions.56-60”
    Quote in the paperSubstantial claim2 of 5 sources checked
    • cites [56] Raine, 1993, Multiple sclerosis: Remyelination in acute lesions, J Neuropathol Exp Neurol source
    • cites [57] Prineas, 1993, Multiple sclerosis: Remyelination of nascent lesions, Ann Neurol source
    • cites [58] Lucchinetti, 1999, A quantitative analysis of oligodendrocytes in multiple sclerosis lesions, Brain source

      The ‘Consequences for remyelination’ section (page unavailable) says remyelination can be extensive early in the formation of some MS lesions and correlates with oligodendrocytes in the lesions. The copy does not establish this specifically for cortical grey matter or place recruitment and remyelination in an immediate post-phagocytic phase while foam cells remain abundant. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [59] Brück, 1994, Oligodendrocytes in the early course of multiple sclerosis, Ann Neurol source
    • cites [60] Prineas, 2023, Microglia subtypes in acute, subacute, and chronic multiple sclerosis, J Neuropathol Exp Neurol. source

      The Results sections on foamy macrophages and subacute MS report remyelination in recently demyelinated tissue alongside foamy macrophages, and oligodendrocyte precursors in recently demyelinated and postphagocytic plaques. They do not establish that this sequence occurs specifically in cortical grey matter or confine it to the immediate post-phagocytic phase. Page numbers are unavailable in our copy. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • Premisecitation

    Data from the cuprizone mouse model and in vivo imaging suggest that satellite oligodendrocytes can generate compact myelin around pyramidal neurons of mouse layer V.

    “data from the cuprizone mouse model and in vivo imaging suggests that these cells can generate compact myelin around pyramidal neurons of mouse layer V.54,55”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [54] Battefeld, 2016, Myelinating satellite oligodendrocytes are integrated in a glial syncytium constraining neuronal high-frequency activity, Nat Commun source

      The Results section (“Identified layer 5 s-OLs myelinate axons”; page not provided) reports that satellite oligodendrocytes beside layer 5 pyramidal neurons form compact myelin around axons. It does not report cuprizone-model data or in vivo imaging; its live imaging was performed during recordings in brain slices. The paper also says these cells did not myelinate the first internode of their host neuron. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [55] Ludwin, 1979, The perineuronal satellite oligodendrocyte, Acta Neuropathol source
  • May combine two claims. 36
  • Classified as probably not a substantial claim. 22
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    In multiple sclerosis, remyelination occurs in both white and grey matter and is more efficient in the cortex than in white matter lesions in the same patient.

    “In patients with multiple sclerosis, remyelination has been observed in both white and grey matter and found to be more efficient in the cortex.”
    • Also stated in: § Introduction · hedged
      “Several neuropathological reports indicate that the cerebral cortex in MS remyelinates more efficiently compared to white matter lesions in the same patient”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [15] Chang, 2012, Cortical remyelination: A new target for repair therapies in multiple sclerosis, Ann Neurol source
    • cites [16] Strijbis, 2017, Cortical remyelination is heterogeneous in multiple sclerosis, J Neuropathol Exp Neurol. source
    • cites [17] Albert, 2007, Extensive cortical remyelination in patients with chronic multiple sclerosis, Brain Pathol source

  • Classified as probably not a substantial claim.

    Premisecitation

    Birth dating of oligodendrocytes by analysis of integrated nuclear bomb test-derived 14C revealed that few oligodendrocytes were newly generated in shadow plaques of multiple sclerosis patients.

    “In addition, birth dating of oligodendrocytes by analysis of integrated nuclear bomb test-derived 14C revealed that few oligodendrocytes were newly generated in shadow plaques of MS patients”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [22] Yeung, 2014, Dynamics of oligodendrocyte generation and myelination in the human brain, Cell source

      The sections “Turnover of myelin and white matter cells in humans” and “Turnover of oligodendrocytes in humans” describe birth dating with nuclear bomb test-derived ¹⁴C and limited oligodendrocyte turnover. They examine corpus callosum and other brain tissue, however; our copy does not report a finding about shadow plaques in multiple sclerosis patients. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Remyelination is a regenerative process of the adult CNS that restores saltatory impulse conduction and trophic support to axons.

    “Remyelination is a crucial regenerative process in demyelinating diseases, limiting persisting damage to the CNS. It restores saltatory nerve conduction and ensures trophic support of axons.”
    • Also stated in: § Introduction · plain
      “Remyelination is a regenerative process of the adult CNS, whereby saltatory impulse conduction and trophic support to axons are restored.”
    Quote in the paperNot a substantial claim3 of 5 sources checked
    • cites [1] Irvine, 2008, Remyelination protects axons from demyelination-associated axon degeneration, Brain source
    • cites [2] Duncan, 2009, Extensive remyelination of the CNS leads to functional recovery, Proc Natl Acad Sci U S A. source

      The Discussion states that remyelination restores fast, secure saltatory conduction, and the introductory passage says it can protect demyelinated fibers against loss. Our copy does not say that remyelination ensures trophic support of axons; protection against loss does not establish that specific mechanism. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [3] Fünfschilling, 2012, Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity, Nature source

      The paper’s Abstract describes oligodendrocyte support of long-term axonal integrity and proposes metabolic support from glia to myelinated axons. It discusses remyelination only as an unlikely explanation for its findings in adult mutant mice; it does not show that remyelination restores saltatory conduction or trophic support in demyelinating disease. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [4] Lee, 2012, Oligodendroglia metabolically support axons and contribute to neurodegeneration, Nature source

      The Introduction (page not provided) says myelin promotes rapid conduction and describes oligodendroglial energy support for axons; the Discussion identifies MCT1-mediated metabolite transport as important to axon function. The paper does not establish that remyelination restores these functions or limits persistent CNS damage in demyelinating diseases. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [5] Lassmann, 1997, Remyelination in multiple sclerosis, Mult Scler source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The efficacy of remyelination depends on multiple factors such as age, disease duration and lesion location.

    “The efficacy of remyelination has been shown to depend on multiple factors such as, age, disease duration and lesion location.”
    Quote in the paperNot a substantial claim4 of 8 sources checked
    • cites [7] Graves, 2023, Ageing and multiple sclerosis, Lancet Neurol source
    • cites [8] Orthmann-Murphy, 2020, Remyelination alters the pattern of myelin in the cerebral cortex, Elife source

      The Results section (‘Layer specific differences in cortical remyelination’; page unavailable) reports that responses to demyelination vary across cortical depths and may affect recovery, supporting a limited role for location. But the Discussion (‘Implications for myelin repair and cognitive function’; page unavailable) says the study examined only the somatosensory cortex of young adult mice and does not know whether replacement varies with age or in other cortical regions. The paper does not establish disease duration as a determinant of remyelination efficacy. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [9] Merkler, 2006, A new focal EAE model of cortical demyelination: Multiple sclerosis-like lesions with rapid resolution of inflammation and extensive remyelination, Brain source
    • cites [10] Snaidero, 2020, Myelin replacement triggered by single-cell demyelination in mouse cortex, Nat Commun source

      The Results section (‘Remyelination is instructed by pre-ablation myelin pattern’; page not provided) shows that cortical remyelination efficiency varies with the pre-existing myelin pattern in mice. It does not show that efficiency depends on age, disease duration, or lesion location, the factors named in the claim. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [11] Patrikios, 2006, Remyelination is extensive in a subset of multiple sclerosis patients, Brain source
    • cites [12] Chang, 2002, Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis, N Engl J Med source
    • cites [13] Sim, 2002, The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation, J Neurosci source

      The paper’s introduction and Discussion report that remyelination becomes less efficient with age, based on comparisons of young and old rats. The Discussion also considers how lesion size and the timing of remyelination after demyelination may affect the process, but it does not establish disease duration or lesion location as determinants of remyelination efficacy. The copy provides no page numbers for these passages. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [14] Kuhlmann, 2008, Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis, Brain source

      The Introduction (page unavailable) contrasts remyelination in early and chronic multiple sclerosis lesions and says that, in most chronic lesions, it is absent or limited to the plaque border. This supports variation with disease stage and within a lesion, but the paper does not establish that remyelination efficacy depends on patient age or anatomical lesion location; its early–chronic comparison also does not establish disease duration as a causal factor. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    MRI studies in people with multiple sclerosis found an inverse correlation of cortical remyelination and cortical atrophy, and an effect on disease progression in a subgroup with less demyelination and shorter disease duration.

    “Recently, MRI studies in people with MS found an inverse correlation of cortical remyelination and cortical atrophy, and an effect on disease progression in a subgroup with less demyelination and shorter disease duration.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [18] Lazzarotto, 2024, Time is myelin: Early cortical myelin repair prevents atrophy and clinical progression in multiple sclerosis, Brain source

  • May combine two claims.

    Premisecitation

    BCAS1+ oligodendrocytes are highly abundant in white matter during developmental myelination but largely disappear in adulthood.

    “BCAS1+ oligodendrocytes are highly abundant in the white matter during developmental myelination but largely disappear in adulthood.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [29] Fard, 2017, BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions, Sci Transl Med source

  • May combine two claims.

    Premisecitation

    BCAS1+ oligodendrocytes in the cortex appear in two main phenotypes: resting cells with few or no immunopositive processes, prevailing in the healthy adult brain, and activated cells with pre-myelinating/myelinating morphology characterized by internode formation.

    “BCAS1+ oligodendrocytes in the cortex appear in two main phenotypes: cells with few or no immunopositive processes, prevailing in the healthy adult brain (‘resting’ BCAS1+ oligodendrocytes; arrows in Fig. 1A) and cells with a pre-myelinating morphology with multiple branches and myelinating morphology, characterized by internode formation (‘activated’ BCAS1+ oligodendrocytes; arrowheads in Fig. 1A”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [31] Kaji, 2020, BCAS1-positive immature oligodendrocytes are affected by the α-synuclein-induced pathology of multiple system atrophy, Acta Neuropathol Commun source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [37] Bergner, 2021, Concurrent axon and myelin destruction differentiates X-linked adrenoleukodystrophy from multiple sclerosis, Glia source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [38] Jiang, 2023, Evaluation of BCAS1-positive immature oligodendrocytes after cerebral ischemic stroke and SVD, Neurosci Lett source

  • May combine two claims.

    Premisecitation

    In the cerebral cortex, the population of BCAS1+ oligodendrocytes remains substantial throughout life and only slowly decreases with age.

    “In contrast, in the cerebral cortex, the population of BCAS1+ oligodendrocytes remains substantial throughout life and only slowly decreases with age.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [29] Fard, 2017, BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions, Sci Transl Med source

  • May combine two claims.

    Premisecitation

    BCAS1+ oligodendrocytes are Olig2+ but do not express markers of oligodendrocyte precursor cells (e.g. NG2) and mature oligodendrocytes (e.g. CC1 or p25/TTTP), representing an intermediate stage of oligodendrocyte differentiation.

    “BCAS1+ oligodendrocytes are Olig2+ but do not express markers of oligodendrocyte precursor cells (e.g. NG2) and mature oligodendrocytes (e.g. CC1 or p25/TTTP), thus representing an intermediate stage of oligodendrocyte differentiation.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [29] Fard, 2017, BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions, Sci Transl Med source

      The Results report that human BCAS1+ cells coexpress OLIG2 and largely lack NG2, CC1, and TPPP/p25, supporting their identification as a distinct differentiation stage (Fig. 5A–B). But the claim's unqualified statement that they do not express these markers overstates the findings: 3.5% of human BCAS1+ cells expressed NG2, while in mice 16.5% expressed NG2 and 76.2% overlapped with CC1 (Results, Fig. 1C). (LLM, conf=0.90)

      Experimental — accuracy not yet measured
    • cites [30] Ishimoto, 2017, Mice lacking BCAS1, a novel myelin-associated protein, display hypomyelination, schizophrenia-like abnormal behaviors, and upregulation of inflammatory genes in the brain, Glia source
    • cites [31] Kaji, 2020, BCAS1-positive immature oligodendrocytes are affected by the α-synuclein-induced pathology of multiple system atrophy, Acta Neuropathol Commun source

      The Introduction identifies BCAS1-positive cells as immature, differentiating oligodendrocytes that express OLIG2 and show limited labeling for precursor and mature-cell markers. The claim overstates this as no expression: the paper reports NG2 labeling in 3.5% of these cells and TPPP/p25α labeling in 0.6%, although CC1 labeling was 0%. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Newly formed cells might be much more efficient compared to surviving oligodendrocytes.

    “and it has been demonstrated that newly formed cells might be much more efficient compared to surviving oligodendrocytes.”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [26] Xing, 2014, Adult neural precursor cells from the subventricular zone contribute significantly to oligodendrocyte regeneration and remyelination, J Neurosci source
    • cites [27] Neely, 2022, New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination, Nat Neurosci source
    • cites [28] Mezydlo, 2023, Remyelination by surviving oligodendrocytes is inefficient in the inflamed mammalian cortex, Neuron source

  • Classified as probably not a substantial claim.

    Premisecitation

    Remyelination after a demyelinating insult is more efficient in the cerebral cortex compared to the white matter.

    “Previous studies in human post-mortem tissue and experimental models suggested that remyelination after a demyelinating insult is more efficient in the cerebral cortex compared to the white matter.”
    • Also stated in: § Discussion · plain
      “cortical remyelination efficacy is prominent when areas of remyelination in cortical and white matter lesions are compared in the same patients.15-17”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [15] Chang, 2012, Cortical remyelination: A new target for repair therapies in multiple sclerosis, Ann Neurol source

      The Results section reports that remyelination was more extensive in the cortical than the white-matter portion of 24 of 28 remyelinated leukocortical lesions, supporting the comparison in human postmortem tissue. The paper’s Methods describe human tissue analysis, not an experimental-model comparison, so it does not support that part of the citing sentence. (LLM, conf=0.82)

      Experimental — accuracy not yet measured
    • cites [16] Strijbis, 2017, Cortical remyelination is heterogeneous in multiple sclerosis, J Neuropathol Exp Neurol. source
    • cites [17] Albert, 2007, Extensive cortical remyelination in patients with chronic multiple sclerosis, Brain Pathol source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The debris-clearing function of myeloid cells and mediators released from innate immune cells stimulate remyelination.

    “This aligns with the notion that the debris-clearing function of myeloid cells and mediators released from innate immune cells stimulate remyelination.61-63”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites [61] Arnett, 2001, TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination, Nat Neurosci source
    • cites [62] Foote, 2005, Inflammation stimulates remyelination in areas of chronic demyelination, Brain source
    • cites [63] Syed, 2016, Antibody-mediated neutralization of myelin-associated EphrinB3 accelerates CNS remyelination, Acta Neuropathol source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Demyelination of cortical grey matter is an important characteristic of MS, and in many patients the proportion of demyelinated grey matter outweighs that of demyelinated white matter.

    “Demyelination of the cortical grey matter is an important characteristic of MS, and the proportion of demyelinated grey matter outweighs that of demyelinated white matter in many patients.46,47”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [46] Kutzelnigg, 2005, Cortical demyelination and diffuse white matter injury in multiple sclerosis, Brain source
    • cites [47] Trapp, 2018, Cortical neuronal densities and cerebral white matter demyelination in multiple sclerosis: A retrospective study, Lancet Neurol source

      The Introduction describes cortical demyelination as a prominent feature of postmortem MS brains. The Discussion reports cortical demyelination without significant cerebral white-matter demyelination in the myelocortical MS subgroup (12 of 97 autopsy cases). It does not establish that the proportion of demyelinated grey matter exceeds that of white matter in many MS patients generally. (LLM, conf=0.83)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The ability of oligodendrocytes and myelin to provide physical protection and metabolic support is undisputed.

    “the ability of oligodendrocytes and myelin to provide physical protection and metabolic support is undisputed.42,43”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [42] Schäffner, 2023, Myelin insulation as a risk factor for axonal degeneration in autoimmune demyelinating disease, Nat Neurosci source

      The Discussion (page not provided) describes oligodendroglial metabolic support of myelinated axons. But it says that “myelin per se does not support axon integrity,” and the Main section challenges the view of myelin as solely protective in autoimmune disease. The unqualified claim that myelin provides undisputed physical protection is therefore not supported. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [43] Franklin, 2024, Remyelination in the central nervous system, Cold Spring Harb Perspect Biol source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The differentiation of local oligodendrocyte progenitor cells into actively myelinating oligodendrocytes is stimulated by innate immune cells.

    “Recent data have indicated that the differentiation of local oligodendrocyte progenitor cells into actively myelinating oligodendrocytes is stimulated by innate immune cells.64-67”
    Quote in the paperNot a substantial claim3 of 4 sources checked
    • cites [64] Miron, 2013, M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination, Nat Neurosci source
    • cites [65] Madsen, 2016, Oligodendroglial TNFR2 mediates membrane TNF-dependent repair in experimental autoimmune encephalomyelitis by promoting oligodendrocyte differentiation and remyelination, J Neurosci source

      The Discussion reports that TNFR2 activation in oligodendrocyte progenitor cells promotes their differentiation and sustains remyelination; the Results section also finds impaired differentiation when TNFR2 is absent. However, the cited passages do not establish that innate immune cells provide the stimulus, and the paper’s purified progenitor-cell cultures contained no microglia. Page numbers were not available in our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [66] Cunha, 2020, Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis, J Exp Med. source
    • cites [67] Franklin, 2022, CNS remyelination and inflammation: From basic mechanisms to therapeutic opportunities, Neuron source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Oligodendrocyte precursor cells in cortex and white matter differ in their propensity for terminal differentiation, and cortical oligodendrocytes reach their final number much later in life than in white matter.

    “oligodendrocyte precursor cells in cortex and white matter were shown to differ in their propensity for terminal differentiation, and cortical oligodendrocytes reach their final number much later in life than in the white matter, as inferred from 14C incorporation.48”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [48] Yeung, 2019, Dynamics of oligodendrocyte generation in multiple sclerosis, Nature source

      The paper reports 14C measurements of oligodendrocytes in white matter (Oligodendrocyte generation dynamics in multiple sclerosis, page unavailable). Searches for cortex, cortical oligodendrocyte numbers, and cortex–white-matter differentiation found no passage comparing those regions or stating when their oligodendrocytes reach their final numbers. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The density of BCAS1+ oligodendrocytes in the cortex remains high throughout life, in contrast to white matter, supporting a physiological role in neuronal function.

    “the density of BCAS1+ oligodendrocytes in the cortex remains high throughout life—in stark contrast to the white matter—supporting a physiological role in neuronal function, e.g. as effectors of adaptive cortical myelination and circuit modulation.49,50”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [49] Gibson, 2014, Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain, Science source

      The Discussion reports that neuronal activity promotes oligodendrocyte formation and myelination in cortical circuits, with associated behavioral improvement. But the paper does not report BCAS1+ cell density or show that it remains high throughout life in cortex relative to white matter. Its density measurements concern newly generated EdU+/CC1+ oligodendrocytes at two mouse ages, not BCAS1+ cells. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [50] McKenzie, 2014, Motor skill learning requires active central myelination, Science source

      The Abstract and “Running stimulates OP proliferation and OL production” section support a role for newly formed oligodendrocytes and myelination in motor learning, and discuss activity-dependent myelination as a possible mechanism. Our copy does not identify BCAS1+ cells or show that their density remains high throughout life in cortex, in contrast to white matter (searched: BCAS1, cortical density, adaptive cortical myelination). No page numbers were available in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Which cells are at the forefront of myelin regeneration is a matter of ongoing debate.

    “Which cells are at the forefront of myelin regeneration is a matter of ongoing debate.44,45”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [44] Franklin, 2021, Revisiting remyelination: Towards a consensus on the regeneration of CNS myelin, Semin Cell Dev Biol. source
    • cites [45] Lubetzki, 2020, Remyelination in multiple sclerosis: From basic science to clinical translation, Lancet Neurol. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Numerical and functional differences in oligodendrocyte lineage cells, and the phenotype of reactive astrogliosis including lower expression of CD44, versican and hyaluronan in the cortex, may play a role in cortical remyelination.

    “Studies in human tissue and experimental models suggest that numerical and functional differences in oligodendrocyte lineage cells, as well as e.g. the phenotype of reactive astrogliosis, including a lower expression of CD44, versican and hyaluronan in the cortex, may play a role.15”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [15] Chang, 2012, Cortical remyelination: A new target for repair therapies in multiple sclerosis, Ann Neurol source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Satellite oligodendrocytes are largely considered non-myelinating and may fulfil specific functions in neuronal support.

    “Satellite oligodendrocytes are largely considered non-myelinating and may fulfil specific functions in neuronal support.51-54”
    Quote in the paperSubstantial claim3 of 4 sources checked
    • cites [51] Takasaki, 2010, Cytochemical and cytological properties of perineuronal oligodendrocytes in the mouse cortex, Eur J Neurosci source
    • cites [52] Szuchet, 2011, The genetic signature of perineuronal oligodendrocytes reveals their unique phenotype, Eur J Neurosci source
    • cites [53] Kruger, 1966, Electron microscopy of oligodendrocytes in normal rat cerebrum, Am J Anat source
    • cites [54] Battefeld, 2016, Myelinating satellite oligodendrocytes are integrated in a glial syncytium constraining neuronal high-frequency activity, Nat Commun source

  • May combine two claims.

    Premisecitation

    Autopsy studies of patients with long-lasting disease show extensive cortical demyelination with severe reduction in oligodendrocyte lineage cells.

    “autopsy studies of patients with long-lasting disease show extensive cortical demyelination with severe reduction in oligodendrocyte lineage cells.41,46,68”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [41] Rodriguez, 2014, Oligodendroglia in cortical multiple sclerosis lesions decrease with disease progression, but regenerate after repeated experimental demyelination, Acta Neuropathol source
    • cites [46] Kutzelnigg, 2005, Cortical demyelination and diffuse white matter injury in multiple sclerosis, Brain source
    • cites [68] Bø, 2009, The histopathology of grey matter demyelination in multiple sclerosis, Acta Neurol Scand Suppl source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Previous experimental and human work suggests that g-ratios are higher and internodes shorter in demyelinated cortex than in normal cortex, without directly associating newly formed internodes to BCAS1 expression.

    “Previous experimental and human work on demyelinated cortex suggests that g-ratios are indeed higher and internodes shorter than in NC, however, without directly associating newly formed internodes to the expression of BCAS1.10,17”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [10] Snaidero, 2020, Myelin replacement triggered by single-cell demyelination in mouse cortex, Nat Commun source

      In Results (page unavailable), newly formed internodes in the mouse cortex had thinner myelin and higher g-ratios than pre-existing internodes. The Discussion (page unavailable) says spontaneously added internodes appeared shorter than pre-existing ones, but Results also says restored internodes were longer than de novo internodes. This paper does not establish the human comparison or directly associate internodes with BCAS1 expression. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [17] Albert, 2007, Extensive cortical remyelination in patients with chronic multiple sclerosis, Brain Pathol source

      The Results report higher g-ratios in remyelinated cortical areas than in control cortex (0.76 versus 0.65). They do not report g-ratios for demyelinated cortex or measure internode length. The paper also does not assess BCAS1 expression or link it to newly formed internodes. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    The number of BCAS1+ oligodendrocytes with activated morphology in mouse cortex increased compared to naïve mice from the beginning of the cuprizone diet, though not significant in the first week.

    “However, when we specifically quantified BCAS1+ oligodendrocytes with activated morphology, we saw a clear increase in myelinating cells compared to naïve mice from the very beginning of the cuprizone diet (though not significant in the first week; Fig. 1C).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The percentage of BCAS1+ satellite cells co-expressing cytosolic MAG showed a tendency to increase from Week 4 under cuprizone treatment, but this was not significant.

    “The percentage of BCAS1+ satellite cells co-expressing cytosolic MAG, which is essential for early oligodendrocyte–axon contact, showed a tendency to increase from Week 4 under treatment, further indicating ongoing formation of novel myelin sheaths (not significant; Fig. 2C).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: MAG is necessary for early oligodendrocyte–axon contact formation.

  • May combine two claims.

    Findingown data

    No change in the total number of satellite oligodendrocytes, of BCAS1+ cells or the percentage of BCAS1+ satellite cells was observed during cuprizone treatment.

    “No change in the total number of satellite oligodendrocytes, of BCAS1+ cells or the percentage of BCAS1+ satellite cells was observed during cuprizone treatment (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The increase in activated BCAS1+ oligodendrocytes reached its maximum at Week 4, when loss of mature TPPP/p25+ oligodendrocytes was severe and still ongoing in the cortex.

    “This increase reached its maximum at a time point when the loss of mature tubulin polimerization promoting protein (TPPP/p25)+ oligodendrocytes was severe and still ongoing in the cortex (Week 4; Fig. 1D).”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    In MS autopsy cortex, TPPP/p25+ oligodendrocyte density was significantly increased in normal-appearing cortex compared to remyelinating cortical lesions and normal cortex.

    “was significantly increased in the normal-appearing cortex compared to remyelinating cortical lesions and normal cortex (Fig. 4E and F)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In chronic multiple sclerosis remyelinating cortical areas, the total number of BCAS1+ oligodendrocytes was not changed compared to control tissue, while it was clearly reduced in fully demyelinated, non-remyelinating cortical lesions.

    “Similar to the observations made in biopsy tissue, the total number of BCAS1+ oligodendrocytes in these remyelinating areas was not changed compared to control tissue, while it was clearly reduced in fully demyelinated, non-remyelinating cortical lesions”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    While only a subpopulation of BCAS1+ oligodendrocytes co-expressed MAG, practically all oligodendrocytes with MAG+ processes were BCAS1+.

    “While only a subpopulation of BCAS1+ oligodendrocytes co-expressed MAG, practically all oligodendrocytes with MAG+ processes were BCAS1+ (data not shown).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The positionally defined subpopulation of BCAS1+ perineuronal satellite oligodendrocytes can assume a myelinating morphology and express MAG in both the mouse cuprizone model and MS lesions.

    “Our study also demonstrated that the positionally defined subpopulation of BCAS1+ perineuronal satellite oligodendrocytes can assume a myelinating morphology and express MAG in both the mouse cuprizone model and MS lesions.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Cuprizone-induced cortical demyelination is a valid model for MS cortical remyelination.

  • May combine two claims.

    Findingown data

    Resting/pre-differentiated cortical BCAS1+ oligodendrocytes develop into internode-forming, MAG-expressing cells via a branched, star-like pre-myelinating phenotype and down-regulate BCAS1 expression upon differentiation to myelin-maintaining oligodendrocytes.

    “Our results indicated that resting resp. pre-differentiated cortical BCAS1+ oligodendrocytes develop into internode-forming, MAG-expressing cells via a branched, star-like pre-myelinating phenotype and down-regulate BCAS1 expression upon differentiation to myelin-maintaining oligodendrocytes.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Cuprizone-induced cortical demyelination is a valid model for MS cortical remyelination.

  • May combine two claims.

    Findingown data

    Pre-differentiated BCAS1+ oligodendrocytes are decreased in later stage MS, potentially impairing the swift and efficient cortical remyelination response observed in early disease.

    “we also demonstrate here that pre-differentiated BCAS1+ oligodendrocytes are decreased in later stage MS, potentially impairing the swift and efficient cortical remyelination response observed in early disease.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The shift from BCAS1+ to mature oligodendrocytes in chronic multiple sclerosis normal-appearing cortex suggests oligodendrocyte differentiation and limited replenishment of BCAS1+ oligodendrocytes in long-standing disease.

    “suggesting oligodendrocyte differentiation and limited replenishment of BCAS1+ oligodendrocytes in long-standing disease.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Part of perineuronal satellite oligodendrocytes are BCAS1+ and contribute to remyelination in human and experimental cortical demyelination.

    “We also demonstrate that part of perineuronal satellite oligodendrocytes are BCAS1+ and contribute to remyelination in human and experimental cortical demyelination.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The cuprizone and antibody-induced mouse models recapitulate key aspects of human cortical demyelination and remyelination.

  • Classified as probably not a substantial claim.

    Premisecitation

    Remyelination is associated with proliferation and differentiation of oligodendrocyte precursor cells into mature oligodendrocytes.

    “Importantly, however, a multitude of experimental evidence has shown that remyelination is associated with proliferation and differentiation of oligodendrocyte precursor cells into mature oligodendrocytes”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [23] Gensert, 1997, Endogenous progenitors remyelinate demyelinated axons in the adult CNS, Neuron source
    • cites [24] Carroll, 1994, Early recruitment of oligodendrocyte precursors in CNS demyelination, Brain source
    • cites [25] Windrem, 2004, Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain, Nat Med source

  • May combine two claims.

    Interpretationown data

    BCAS1+ cells in the adult cortex represent a population of pre-differentiated oligodendrocytes that rapidly react after a demyelinating insult, enabling immediate myelin regeneration.

    “In summary, our results provide evidence from human tissue and experimental models that BCAS1+ cells in the adult cortex represent a population of pre-differentiated oligodendrocytes that rapidly react after a demyelinating insult thus enabling immediate myelin regeneration.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The cuprizone and antibody-induced mouse models recapitulate key aspects of human cortical demyelination and remyelination.

  • May combine two claims.

    Interpretationown data

    Successful cortical remyelination occurs in areas with normal densities of BCAS1+ oligodendrocytes, from which internode-forming activated BCAS1+ cells can be recruited.

    “Our data so far indicated that successful cortical remyelination occurs in areas with normal densities of BCAS1+ oligodendrocytes, from which internode-forming, activated BCAS1+ cells can be recruited.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Previous differentiation stimuli, e.g. demyelination and inflammation, might lead to a reduction in BCAS1+ oligodendrocytes in the cortex if they are not sufficiently replenished by the proliferation and differentiation of oligodendrocyte precursor cells.

    “Thus, previous differentiation stimuli, e.g. demyelination and inflammation, might lead to a reduction in BCAS1+ oligodendrocytes in the cortex, if they are not sufficiently replenished by the proliferation and differentiation of oligodendrocyte precursor cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    BCAS1+ cells represent a transitional stage of oligodendrocyte differentiation between oligodendrocyte progenitor cells and myelin-maintaining oligodendrocytes, and their differentiation fills up or adds to the population of TPPP/p25 mature oligodendrocytes.

    “As BCAS1+ cells represent a transitional stage of oligodendrocyte differentiation between oligodendrocyte progenitor cells and myelin-maintaining oligodendrocytes, their differentiation fills up or adds to the population of TPPP/p25 mature oligodendrocytes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Activated BCAS1+ oligodendrocytes in the cortex are generated early after lesion initiation and amidst ongoing toxic oligodendrocyte loss and myelin phagocytosis.

    “Our experimental data suggested that activated BCAS1+ oligodendrocytes in the cortex are generated early after lesion initiation and amidst ongoing toxic oligodendrocyte loss (cuprizone) and myelin phagocytosis (antibody-induced demyelination).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The cuprizone and antibody-induced mouse models recapitulate key aspects of human cortical demyelination and remyelination.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study was approved by the local ethics committee.

    “The study was approved by the local ethics committee.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The increase in TPPP/p25+ and decrease in BCAS1+ in normal-appearing cortex of long-standing MS may indicate a shift from BCAS1+ to TPPP/p25+ oligodendrocytes and chronic exposure to differentiating stimuli, likely associated with chronic inflammation.

    “This may indicate a shift from BCAS1+ to TPPP/p25+ oligodendrocytes in the normal-appearing cortex of long-standing MS and hint towards a chronic exposure to differentiating stimuli, most likely associated with chronic inflammation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Cortical BCAS1+ oligodendrocytes contribute to remyelination after a demyelinating insult to the cortex and may constitute a quiescent population of pre-differentiated oligodendrocytes that serves as a reservoir for swift and efficient myelin regeneration.

    “This suggested that cortical BCAS1+ oligodendrocytes contribute to remyelination after a demyelinating insult to the cortex and may constitute a ‘quiescent’ population of pre-differentiated oligodendrocytes that serves as a reservoir for swift and efficient myelin regeneration.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Cuprizone-induced cortical demyelination is a valid model for MS cortical remyelination.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationnone given

    Satellite oligodendrocytes sense neuronal electric and metabolic activity, putting them in an ideal position to react rapidly to changing metabolic and circuitry demands.

    “Importantly, satellite oligodendrocytes sense neuronal electric and metabolic activity, thus putting them into an ideal position to react rapidly to changing metabolic and circuitry demands.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    While there is a higher propensity to remyelinate in early disease, failure of repair ensues if further and long-lasting damage is imposed on the cortex, eventually resulting in persisting demyelination as observed in autopsy tissue of later stage disease.

    “Thus, while we observe a higher propensity to remyelinate in early disease, failure of repair ensues if further and long-lasting damage is imposed on the cortex, eventually resulting in persisting demyelination, as frequently observed in autopsy tissue of later stage disease.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Cortical BCAS1+ oligodendrocytes, in part localized in a perineuronal satellite position, engage in remyelination in demyelinating models and human biopsy and autopsy tissue from patients with MS.

    “In the present work, we demonstrated that cortical BCAS1+ oligodendrocytes, in part localized in a perineuronal satellite position, engage in remyelination in demyelinating models and human biopsy and autopsy tissue from patients with MS.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Cuprizone-induced cortical demyelination is a valid model for MS cortical remyelination.

  • May combine two claims.

    Interpretationown data

    BCAS1+ oligodendrocytes are activated early after demyelination in MS lesions and differentiate to BCAS1+ cells with pre- and myelinating morphology to generate new myelin, while total BCAS1+ oligodendrocyte number remains unchanged.

    “These cells are activated early after demyelination in MS lesions and differentiate to BCAS1+ cells with a pre- and myelinating morphology to generate new myelin, while the total number of BCAS1+ oligodendrocytes remains unchanged.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Cuprizone-induced cortical demyelination is a valid model for MS cortical remyelination.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    In the cortex, such damage could cause premature terminal differentiation of early oligodendrocyte developmental stages serving immediate tissue repair.

    “In the cortex, such damage could cause premature terminal differentiation of early oligodendrocyte developmental stages serving immediate tissue repair.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The shift towards more mature oligodendrocyte subsets may reflect previous stimulation of oligodendroglial differentiation in normal-appearing cortex in disease, with differentiation of BCAS1+ oligodendrocytes, including satellite cells, to myelin-maintaining oligodendrocytes.

    “This may reflect previous stimulation of oligodendroglial differentiation in the normal-appearing cortex in the context of disease, with differentiation of BCAS1+ oligodendrocytes, including satellite cells, to myelin-maintaining oligodendrocytes (Fig. 6).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The stimulation of differentiation by innate immune cells may also be true for the quiescent population of pre-differentiated BCAS1+ oligodendrocytes.

    “This may also be true for the quiescent population of pre-differentiated BCAS1+ oligodendrocytes.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Increased densities of TPPP/p25 myelin-maintaining oligodendrocytes have previously been demonstrated in normal-appearing white matter in autopsy tissue of patients with chronic MS.

    “increased densities of TPPP/p25 myelin-maintaining oligodendrocytes have previously been demonstrated in the normal-appearing white matter in autopsy tissue of patients with chronic MS.69”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [69] Höftberger, 2010, Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis, Glia source
51 of 51

  • The paper relies on this without support.

    MAG is necessary for early oligodendrocyte–axon contact formation.

    “co-expressing myelin-associated glycoprotein (MAG), necessary for axonal contact formation.”
    “MAG, which is essential for early oligodendrocyte–axon contact”

  • The paper relies on this without support.

    The cuprizone and antibody-induced mouse models recapitulate key aspects of human cortical demyelination and remyelination.

    “in direct comparison to demyelinating mouse models”
    “whether this early increase in activated BCAS1+ oligodendrocytes, found in the cortex under conditions of toxic oligodendrocyte damage, is a general feature of cortical demyelinating lesions and can also be observed in an animal model of antibody-mediated demyelination.”

  • The paper relies on this without support.

    Olig2 immunostaining marks all cells of the oligodendrocyte lineage.

    “the total number of Olig2+ cells, representing all cells of the oligodendrocyte lineage, was found to be unaltered”
    “the density of Olig2+ cells, reflecting the entire oligodendroglial lineage, remained unperturbed.”

  • The paper relies on this without support.

    Cuprizone-induced cortical demyelination is a valid model for MS cortical remyelination.

    “We have shown that BCAS1+ satellite oligodendrocytes contribute to remyelination in cuprizone-induced cortical demyelination.”
    “in both the mouse cuprizone model and MS lesions.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Actively myelinating oligodendrocytes are responsible for the ongoing formation and repair of myelin during the demyelinating process observed in multiple sclerosis and multiple system atrophy.

    “Actively myelinating oligodendrocytes are responsible for the ongoing formation and repair of myelin during the demyelinating process observed in multiple sclerosis and multiple system atrophy. 29 , 30”

    From Apolipoprotein ε4 exacerbates white matter impairment in a mouse model of Aβ amyloidosis by decreasing actively myelinating oligodendrocytes (2025) · cites this paper as [30]

    The Abstract and Discussion report that actively myelinating BCAS1-positive oligodendrocytes participate in cortical myelin repair in multiple sclerosis. The paper does not establish that they perform this role in multiple system atrophy; that condition appears in the title of a cited work in the References, which does not substantiate the repair claim. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Median time to biopsy is below the reported first quartile

    Minor

    The reported first quartile of 0.5 years is 6 months, which is greater than the reported median of 3 months. A first quartile cannot exceed the median for the same patients.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. del Rio Hortega, 1942, La neuroglía normal. Conceptos de neurogliona y angiogliona, Arch Histol Norm Patol, 1, 5

Cited by

Sorted by citations

Related

Authors
Bergner, C. G., van der Meer, F., Franz, J., Vakrakou, A., Würfel, T., Nessler, S., Schäfer, L., Nau-Gietz, C., Winkler, A., Lagumersindez-Denis, N., Wrzos, C., Damkou, I. A., Sergiou, C., Schultz, V., Knauer, C., Metz, I., Bahn, E., Garea Rodriguez, E., Merkler, D., Simons, M., & Stadelmann, C.
Affiliations
  • Universitätsmedizin Göttingen (DE)
  • Department of Neuropathology, University Medical Center Göttingen , Göttingen 37075 ,
  • National and Kapodistrian University of Athens (GR)
  • University Hospital Leipzig (DE)
  • Institute of Neuronal Cell Biology, Technical University Munich , Munich 81377 ,
  • University of Geneva (CH)
  • German Center for Neurodegenerative Diseases (DE)
Corresponding author
Stadelmann, Christine
ORCID
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
2024-09-25
Volume
148
Issue
3
Pages
908-920
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/awae293
PMC
PMC11884765
OpenAlex
W4402841138
Semantic Scholar
ef100c15e64fc913b5dfadf2a8f67b27791a85ba
Cited by
16
References
69
Citations by year
2026: 8 · 2025: 7 · 2024: 1
FWCI
4.21
Type
journal article
Language
en
Open access
Licence
Locations
  • Brain (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (publishedVersion, other-oa)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
  • Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by-nc)
  • DZNE Pub (submittedVersion, cc-by-nc)
  • PubMed Central (submittedVersion, cc-by-nc)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by-nc)
Funders
  • Deutsche Forschungsgemeinschaft (408885537, 2067/1- 390729940)
  • Gemeinnützige Hertie-Stiftung
  • Deutschen Multiple Sklerose Gesellschaft
  • National Multiple Sclerosis Society
  • Ministry for Science and Culture of Lower Saxony
  • University Medical Center Göttingen
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
BCAS1, oligodendrocytes, remyelination, multiple sclerosis, cortical demyelination, myelin-associated glycoprotein, oligodendrocyte differentiation, remyelination failure, myeloid cells
MeSH terms
Remyelination, Adult, Aged, Animals, Cerebral Cortex, Disease Models, Animal, DNA-Binding Proteins, Female, Humans, Male, Mice, Inbred C57BL, Middle Aged, Multiple Sclerosis, Myelin Sheath, Nerve Tissue Proteins, Oligodendroglia, Transcription Factors, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-13.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-13.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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