ArticleNature metabolism2025
Cholesterol metabolic reprogramming mediates microglia-induced chronic neuroinflammation and hinders neurorestoration following stroke.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The trial behind it
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Who cites it
31 citing papers in PubMed.
- Molecular Editing Reveals a Bilobalide Chemotype that Attenuates Prolyl Endopeptidase (PREP)-Linked Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cholesterol Drives IFITM3CNS neuroscience & therapeutics · 2026Article
- Membrane-camouflaged metal-phenolic nanomedicines for the treatment of ischemic stroke via relieving oxidative stress and neuroinflammation.Materials today. Bio · 2026Article
- PLIN2-PGAM5-regulated lipid droplet-mitochondria contacts drive microglial neuroinflammation after spinal cord injury via fatty acid metabolic reprogramming.Cell death and differentiation · 2026Article
- Mediation effect of TyG-BMI, LDL-C, and CRP on physical activity-stroke risk relationship.Scientific reports · 2026Article
- Analytical Methods and Application of Single-Cell and Single-Nucleus Transcriptomics in the Study of Ischemic Stroke.Biomolecules · 2026Review
- Vespakinin-M delineates an AMPK/mTOR-arginine-TCA cycle axis to act as an immunometabolic switch in post-stroke microglia.Redox biology · 2026Article
- Microglial Mitochondrial Dysfunction: The Storm Center of Post-Stroke Neuroinflammation.CNS neuroscience & therapeutics · 2026Review
- Lipidomic signatures of CNS ischemic injury and their modulation by immunomodulatory hydrogels.The Analyst · 2026Article
- Article
- A Biomarker Out of Context: Understanding High p-tau217 in the Developing Brain.Molecular neurobiology · 2026Review
- CYP46A1 activation by low-dose efavirenz uncovers the link between brain cholesterol metabolism, energetics, and vasculature.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- CYP46A1-Targeted Treatment Alleviates Long-Term White Matter Injury Following Traumatic Brain Injury by Promoting Cholesterol Metabolic Clearance and Remyelination.CNS neuroscience & therapeutics · 2026Article
- An unrecognized mechanism of neuroprotection by microglial TIA1-mediated stress granules to prevent neuroinflammation and demyelination in experimental autoimmune encephalomyelitis mice through sequestering ApoE mRNA.Journal of neuroinflammation · 2026Article
- The hypoxia-inflammation cycle as a key mechanism of smoldering inflammation and progression in multiple sclerosis.Acta neuropathologica · 2026Review
- Microglial cholesterol reprogramming drives cognitive impairment under hypobaric hypoxia.Journal of neuroinflammation · 2026Article
- Microglial Innate Immune Memory: Implications and Research Advances in Central Nervous System Disorders.Current issues in molecular biology · 2026Review
- Targeting microglial C1q alleviates blood-brain barrier disruption in the thalamus after cortical infarction.Journal of neuroinflammation · 2026Article
- Integrated Transcriptomics and Machine Learning Reveal Lipid Metabolism Related Genes in Ischemic Stroke.Journal of molecular neuroscience : MN · 2026Article
- Microglial NCAM1 attenuates ischemic brain injury by inhibiting NF-κB-driven neuroinflammation through IκBα stabilization.Journal of neuroinflammation · 2026Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Chronic neuroinflammation is a major obstacle to post-stroke recovery, yet the underlying mechanisms, particularly the link between prolonged microglial activation and cholesterol metabolism, are not fully known. Here we show that ischaemic injury induces persistent microglial activation that perpetuates chronic inflammation, leading to microglial cholesterol accumulation and metabolic reprogramming. Using single-cell RNA sequencing, we identified distinct stroke-associated foamy microglia clusters characterized by extensive reprogramming of cholesterol metabolism. Furthermore, direct intracerebral free cholesterol or cholesterol crystal infusion recapitulated sustained microglial activation, directly linking aberrant cholesterol metabolism to prolonged neuroinflammatory responses. Therapeutically, we demonstrate that reducing microglial cholesterol overload through genetic or pharmacological activation of CYP46A1 in male mice promotes white matter repair and functional recovery. These findings highlight microglial cholesterol metabolism as a key driver of post-stroke inflammation, offering therapeutic strategies targeting cholesterol metabolism to mitigate long-term brain damage and promote neurorestoration, potentially improving stroke-related disability outcomes.
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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.