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Cited by 4Neuroinflammation and Neurodegeneration MechanismsAcute Ischemic Stroke ManagementIntracerebral and Subarachnoid Hemorrhage Research

Tet2-mediated clonal hematopoiesis modestly improves neurological deficits and is associated with inflammation resolution in the subacute phase of experimental stroke

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Evans, Megan A., Chavkin, Nicholas W., Sano, Soichi, Sun, Hanna, Sardana, Taneesha, Ravi, Ramya, Doviak, Heather, Wang, Ying +6 more·2024·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2024.1487867PMC PMC11685025
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Abstract

Introduction: Recent work has revealed that clonal hematopoiesis (CH) is associated with a higher risk of numerous age-related diseases, including ischemic stroke, however little is known about whether it influences stroke outcome independent of its widespread effects on cardiovascular disease. Studies suggest that leukocytes carrying CH driver mutations have an enhanced inflammatory profile, which could conceivably exacerbate brain injury after a stroke. Methods: Using a competitive bone marrow transplant model of Tet2-mediated CH, we tested the hypothesis that CH would lead to a poorer outcome after ischemic stroke by augmenting brain inflammation. Stroke was induced in mice by middle cerebral artery occlusion and neurological outcome was assessed at acute (24 h) and subacute (14 d) timepoints. Brains were collected at both time points for histological, immunofluorescence and gene expression assays. Results: Unexpectedly, Tet2-mediated CH had no effect on acute stroke outcome but led to a reduction in neurological deficits during the subacute phase. This improved neurological outcome was associated with lower levels of brain inflammation as evidenced by lower transcript levels of various inflammatory molecules alongside reduced astrogliosis. Discussion: These findings suggest that Tet2-mediated CH may have beneficial effects on outcome after stroke, contrasting with the conventional understanding of CH whereby leukocytes with driver mutations promote disease by exacerbating inflammation.

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Authors
Evans, M. A., Chavkin, N. W., Sano, S., Sun, H., Sardana, T., Ravi, R., Doviak, H., Wang, Y., Yura, Y., Polizio, A. H., Horitani, K., Ogawa, H., Hirschi, K. K., & Walsh, K.
Affiliations
University of Virginia (US)
Corresponding author
Walsh, Kenneth
ORCID
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2024-12-17
Volume
18
Pages
1487867-1487867
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2024.1487867
PMC
PMC11685025
OpenAlex
W4405482266
Cited by
4
References
6
Citations by year
2026: 3 · 2025: 1
FWCI
0.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Aeronautics and Space Administration (80NSSC21K0549)
  • American Heart Association (20POST35210098)
  • Nuclear Safety and Security Commission
  • National Institutes of Health (CA044579, HL142650, AG073249)
  • National Institute on Aging (R01AG073249)
  • National Heart, Lung, and Blood Institute (R01HL152174, R01HL142650)
  • National Cancer Institute (CA044579, P30CA044579)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
Keywords
clonal hematopoiesis, TET2, ischemic stroke, neurological deficit, neuroinflammation, subacute phase, middle cerebral artery occlusion, astrocyte activation, inflammatory gene expression, stroke outcome

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.

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.

What counts as a claim ›How we measure confidence ›How we check this ›

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