Evidence mapPaperPMID 42578421Full record

ArticleCNS neuroscience & therapeutics2026

Cholesterol Drives IFITM3

Yue Cheng, Yuxi Zhou, Yonghui Chen, Tianni Shen, Yan Li, Chen Chen, Qiuyue Fan, Jie Qi, Peiying Li, Yueman Zhang

Abstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Yue ChengDepartment of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID https://orcid.org/0009-0009-9169-7707
Yuxi ZhouDepartment of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID https://orcid.org/0009-0001-5641-235X
Yonghui ChenDepartment of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tianni ShenDepartment of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yan LiDepartment of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chen ChenDepartment of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qiuyue FanDepartment of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jie QiDepartment of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Peiying LiDepartment of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID https://orcid.org/0000-0002-5721-9914
Yueman ZhangDepartment of Anesthesiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID https://orcid.org/0000-0002-8187-3350

Funding

China Postdoctoral Science Foundation 2025M782150Fundamental Research Funds for the Central Universities 25X010202804National Natural Science Foundation of China 82525023National Natural Science Foundation of China U22A20295National Natural Science Foundation of China W2411087Postdoctoral Fellowship Program of CPSF GZC20261294Shanghai Engineering Research Center of Peri-operative Organ Support and Function Preservation 20DZ2254200
6 · The paper itself

Abstract

aimsCerebral ischemic stroke triggers extensive neuronal membrane breakdown, releasing a massive load of cholesterol that overwhelms resident microglia. Dysregulated microglial cholesterol metabolism has been implicated in post-stroke neuroinflammation, yet the specific pathogenic microglial subpopulations, their molecular signatures, and the downstream inflammatory cascades remain poorly defined.

methodsWe employed a permanent distal middle cerebral artery occlusion (dMCAO) model combined with single-cell RNA sequencing (scRNA-seq) to profile immune cell transcriptomes and identify cholesterol-associated microglial markers. Cholesterol dynamics, lipid droplet accumulation, and inflammatory marker expression were quantified via immunofluorescence and transmission electron microscopy. Therapeutic interventions included pharmacological cholesterol mobilization with 2-hydroxypropyl-β-cyclodextrin (HβCD), pharmacological STING inhibition with C-176, and microglia-targeted STING knockdown using AAV9 vectors. Cerebral injury and neurological function were assessed through infarct volume measurement, white matter integrity analysis, and behavioral assays (rotarod and grip strength) in dMCAO, tMCAO, and perioperative stroke (PIS) models.

resultsUsing scRNA-seq, we identified interferon-induced transmembrane protein 3 (IFITM3) as a specific marker for a microglial subpopulation that was characterized by upregulated ACAT1, enhanced cholesterol esterification, and accumulation of cholesterol crystals and lipid droplets. This IFITM3

conclusionIFITM3

Indexed as

CholesterolIschemic StrokeMembrane ProteinsMicrogliaNeuroinflammatory DiseasesRNA-Binding ProteinsAnimalscGAS-STING Signaling PathwayInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLSTING ProteinCholesterolMembrane ProteinsRNA-Binding ProteinsSting1 protein, mouseSTING Proteincholesterolischemic strokemicroglianeuroinflammationSTING

Identifiers

PMID42578421
PMCPMC13459068

What Socratic holds

Textmetadata
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Registered trials

None linked

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.