Evidence map›Paper›PMID 38299349›Full record

ArticleStroke2024

Microglial TLR4 Mediates White Matter Injury in a Combined Model of Diesel Exhaust Exposure and Cerebral Hypoperfusion.

Kristina Shkirkova, Alexandra N Demetriou, Saman Sizdahkhani, Krista Lamorie-Foote, Hongqiao Zhang, Manuel Morales, Selena Chen, Lifu Zhao, Arnold Diaz, Jose A Godoy-Lugo and 9 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stroke, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
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

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.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. White matter injury after brain ischemia.Experimental neurology · 2026
    Review
  4. Targeting the intestinal TLR4-GABAJournal of neuroinflammation · 2026
    Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Air pollution amyloidogenesis is attenuated by the gamma-secretase modulator GSM-15606.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  10. Article
  11. Inhaled Pollutants of the Gero-Exposome and Later-Life Health.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024
    Review
4 · The record

Corrections and comments

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

19 authors at 4 institutions in 3 countries.

Kristina Shkirkova *Zilkha Neurogenetic Institute (K.S., A.N.D., S.S., K.L.-F., M.M., S.C., L.Z., W.J.M.), University of Southern California, Los Angeles.ORCID 0000-0002-9288-4258
Alexandra N Demetriou *Zilkha Neurogenetic Institute (K.S., A.N.D., S.S., K.L.-F., M.M., S.C., L.Z., W.J.M.), University of Southern California, Los Angeles.ORCID 0000-0002-9002-3593
Saman Sizdahkhani *Zilkha Neurogenetic Institute (K.S., A.N.D., S.S., K.L.-F., M.M., S.C., L.Z., W.J.M.), University of Southern California, Los Angeles.
Krista Lamorie-FooteZilkha Neurogenetic Institute (K.S., A.N.D., S.S., K.L.-F., M.M., S.C., L.Z., W.J.M.), University of Southern California, Los Angeles.
Hongqiao ZhangLeonard Davis School of Gerontology (H.Z., A.D., J.A.G.-L., B.Z., N.Z., A.L., M.A.T., C.E.F., C.P.), University of Southern California, Los Angeles.
Manuel MoralesZilkha Neurogenetic Institute (K.S., A.N.D., S.S., K.L.-F., M.M., S.C., L.Z., W.J.M.), University of Southern California, Los Angeles.ORCID 0000-0001-7940-8743
Selena ChenZilkha Neurogenetic Institute (K.S., A.N.D., S.S., K.L.-F., M.M., S.C., L.Z., W.J.M.), University of Southern California, Los Angeles.
Lifu ZhaoZilkha Neurogenetic Institute (K.S., A.N.D., S.S., K.L.-F., M.M., S.C., L.Z., W.J.M.), University of Southern California, Los Angeles.
Arnold DiazLeonard Davis School of Gerontology (H.Z., A.D., J.A.G.-L., B.Z., N.Z., A.L., M.A.T., C.E.F., C.P.), University of Southern California, Los Angeles.ORCID 0009-0005-7047-8776
Jose A Godoy-LugoLeonard Davis School of Gerontology (H.Z., A.D., J.A.G.-L., B.Z., N.Z., A.L., M.A.T., C.E.F., C.P.), University of Southern California, Los Angeles.ORCID 0000-0003-4671-3201
Beryl ZhouLeonard Davis School of Gerontology (H.Z., A.D., J.A.G.-L., B.Z., N.Z., A.L., M.A.T., C.E.F., C.P.), University of Southern California, Los Angeles.
Nathan ZhangLeonard Davis School of Gerontology (H.Z., A.D., J.A.G.-L., B.Z., N.Z., A.L., M.A.T., C.E.F., C.P.), University of Southern California, Los Angeles.ORCID 0000-0003-3111-5794
Andrew LiLeonard Davis School of Gerontology (H.Z., A.D., J.A.G.-L., B.Z., N.Z., A.L., M.A.T., C.E.F., C.P.), University of Southern California, Los Angeles.ORCID 0000-0003-3749-3243
Wendy J MackZilkha Neurogenetic Institute (K.S., A.N.D., S.S., K.L.-F., M.M., S.C., L.Z., W.J.M.), University of Southern California, Los Angeles.ORCID 0000-0002-2474-7921
Constantinos SioutasViterbi School of Engineering (C.S.), University of Southern California, Los Angeles.ORCID 0000-0001-5146-0857
Max A ThorwaldLeonard Davis School of Gerontology (H.Z., A.D., J.A.G.-L., B.Z., N.Z., A.L., M.A.T., C.E.F., C.P.), University of Southern California, Los Angeles.ORCID 0000-0003-0095-5344
Caleb E FinchLeonard Davis School of Gerontology (H.Z., A.D., J.A.G.-L., B.Z., N.Z., A.L., M.A.T., C.E.F., C.P.), University of Southern California, Los Angeles.
Christian PikeLeonard Davis School of Gerontology (H.Z., A.D., J.A.G.-L., B.Z., N.Z., A.L., M.A.T., C.E.F., C.P.), University of Southern California, Los Angeles.ORCID 0000-0003-4577-7668
William J MackORCID 0000-0003-0970-2546
Anna Needs Neuroblastoma Answers · USUniversity of Southern California · USNorwegian Womens Public Health Association · NOPharmacoGenetics (China) · CN

Funding

USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI · 2020 to 2026
$27.8M
Urban Air Pollution and Pathological Brain Aging: A Nationwide Twin Study in MenP01AG055367 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MACK, WILLIAM J · 2018 to 2022
$11.5M
NIA NIH HHS P01 AG055367NIA NIH HHS P30 AG066530
6 · The paper itself

Abstract

backgroundAir pollution particulate matter exposure and chronic cerebral hypoperfusion (CCH) contribute to white matter toxicity through shared mechanisms of neuroinflammation, oxidative stress, and myelin breakdown. Prior studies showed that exposure of mice to joint particulate matter and CCH caused supra-additive injury to corpus callosum white matter. This study examines the role of TLR4 (toll-like receptor 4) signaling in mediating neurotoxicity and myelin damage observed in joint particulate matter and CCH exposures.

methodsExperiments utilized a novel murine model of inducible monocyte/microglia-specific TLR4 knockout (i-mTLR4-ko). Bilateral carotid artery stenosis (BCAS) was induced surgically to model CCH. TLR4-intact (control) and i-mTLR4-ko mice were exposed to 8 weeks of either aerosolized diesel exhaust particulate (DEP) or filtered air (FA) in 8 experimental groups: (1) control/FA (n=10), (2) control/DEP (n=10), (3) control/FA+BCAS (n=9), (4) control/DEP+BCAS (n=10), (5) i-mTLR4-ko/FA (n=9), (6) i-mTLR4-ko/DEP (n=8), (7) i-mTLR4-ko/FA+BCAS (n=8), and (8) i-mTLR4-ko/DEP+BCAS (n=10). Corpus callosum levels of 4-hydroxynonenal, 8-Oxo-2'-deoxyguanosine, Iba-1 (ionized calcium-binding adapter molecule 1), and dMBP (degraded myelin basic protein) were assayed via immunofluorescence to measure oxidative stress, neuroinflammation, and myelin breakdown, respectively.

resultsCompared with control/FA mice, control/DEP+BCAS mice exhibited increased dMBP (41%;

conclusionsi-mTLR4-ko markedly reduced neuroinflammation and oxidative stress and attenuated white matter degradation following DEP and CCH exposures. This suggests a potential role for targeting TLR4 signaling in individuals with vascular cognitive impairment, particularly those exposed to substantial ambient air pollution.

Indexed as

AldehydesBrain IschemiaCarotid StenosisWhite Matter8-Hydroxy-2'-DeoxyguanosineAnimalsMiceMice, Inbred C57BLMicrogliaNeuroinflammatory DiseasesParticulate MatterToll-Like Receptor 4Vehicle Emissions4-hydroxy-2-nonenal8-Hydroxy-2'-DeoxyguanosineAldehydesParticulate MatterToll-Like Receptor 4Vehicle Emissionscarotid stenosismicemicrogliatoll-like receptor 4white matter

Identifiers

PMID38299349
PMCPMC10978264
OpenAlexW4391447941

What OpenQuestion holds

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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 OpenQuestion graph.