ArticleBrain pathology (Zurich, Switzerland)2023
Peripheral macrophages drive CNS disease in the Ndufs4(-/-) model of Leigh syndrome.
Article in Brain pathology (Zurich, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Mitochondrial DNA release and inflammation in mitochondrial disease pathogenesis.Brain : a journal of neurology · 2026Review
- Mechanisms and disease relevance of mitochondrial translation in humans.Nature reviews. Molecular cell biology · 2026Review
- Neurodegenerative Diseases in Children: A Comprehensive Review.International journal of molecular sciences · 2026Review
- Leigh Syndrome Pathomechanism Involves Region-Specific Innate Immune Activation in Ndufs4 Knockout Mice.Cellular and molecular neurobiology · 2026Article
- Pharmacological Depletion of Retinal Mononuclear Phagocytes Is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy.Investigative ophthalmology & visual science · 2026Article
- An inherited mitochondrial DNA mutation remodels inflammatory cytokine responses in macrophages and in vivo in mice.Nature communications · 2025Article
- Evaluating the efficacy of vatiquinone in preclinical models of Leigh syndrome and GPX4 deficiency.Orphanet journal of rare diseases · 2025Article
- Disruption of adaptive immunity does not attenuate disease in the Ndufs4(-/-) model of Leigh syndrome.PloS one · 2025Article
- Evaluating the efficacy of vatiquinone in preclinical models of mitochondrial disease.Research square · 2024Article
- Interferon-gamma contributes to disease progression in the Ndufs4(-/-) model of Leigh syndrome.Neuropathology and applied neurobiology · 2024Article
- The Blood-Brain Barrier Is Unaffected in theInternational journal of molecular sciences · 2024Article
- Interleukin-6-elicited chronic neuroinflammation may decrease survival but is not sufficient to drive disease progression in a mouse model of Leigh syndrome.Journal of inflammation (London, England) · 2024Article
- Peripheral macrophages drive CNS disease in the Ndufs4(-/-) model of Leigh syndrome.Brain pathology (Zurich, Switzerland) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Subacute necrotizing encephalopathy, or Leigh syndrome (LS), is the most common pediatric presentation of genetic mitochondrial disease. LS is a multi-system disorder with severe neurologic, metabolic, and musculoskeletal symptoms. The presence of progressive, symmetric, and necrotizing lesions in the brainstem are a defining feature of the disease, and the major cause of morbidity and mortality, but the mechanisms underlying their pathogenesis have been elusive. Recently, we demonstrated that high-dose pexidartinib, a CSF1R inhibitor, prevents LS CNS lesions and systemic disease in the Ndufs4(-/-) mouse model of LS. While the dose-response in this study implicated peripheral immune cells, the immune populations involved have not yet been elucidated. Here, we used a targeted genetic tool, deletion of the colony-stimulating Factor 1 receptor (CSF1R) macrophage super-enhancer FIRE (Csf1rΔFIRE), to specifically deplete microglia and define the role of microglia in the pathogenesis of LS. Homozygosity for the Csf1rΔFIRE allele ablates microglia in both control and Ndufs4(-/-) animals, but onset of CNS lesions and sequalae in the Ndufs4(-/-), including mortality, are only marginally impacted by microglia depletion. The overall development of necrotizing CNS lesions is not altered, though microglia remain absent. Finally, histologic analysis of brainstem lesions provides direct evidence of a causal role for peripheral macrophages in the characteristic CNS lesions. These data demonstrate that peripheral macrophages play a key role in the pathogenesis of disease in the Ndufs4(-/-) model.
Indexed as
Identifiers
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.