Evidence map›Paper›PMID 39903369›Full record

ArticleGeroScience2025

Inhibition of soluble epoxide hydrolase ameliorates cerebral blood flow autoregulation and cognition in alzheimer's disease and diabetes-related dementia rat models.

Chengyun Tang, Jane J Border, Huawei Zhang, Andrew Gregory, Shan Bai, Xing Fang, Yedan Liu, Shaoxun Wang, Sung Hee Hwang, Wenjun Gao and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in GeroScience, 2025. 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
–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

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.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

Chengyun Tang *Physiology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Jane J Border *Pharmacology &Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Huawei Zhang *Pharmacology &Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Andrew GregoryPhysiology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Shan BaiCenter for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Xing FangPharmacology &Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Yedan LiuPharmacology &Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Shaoxun WangPharmacology &Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Sung Hee HwangEntomology and Nematology and UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, USA.
Wenjun GaoPharmacology &Toxicology, University of Mississippi Medical Center, Jackson, MS, USA.
Gilbert C MorganPhysiology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Jhania SmithPhysiology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
David BunnPhysiology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Cameron CantwellPhysiology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Karen M WagnerEntomology and Nematology and UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, USA.
Christophe MorisseauEntomology and Nematology and UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, USA.
Jun YangEntomology and Nematology and UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, USA.
Seung Min ShinAnesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Philip O'HerronPhysiology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Zsolt BagiPhysiology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Jessica A FilosaPhysiology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Yanbin DongGeorgia Prevention Center, Augusta University, Augusta, GA, USA.
Hongwei YuAnesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Bruce D HammockEntomology and Nematology and UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, USA.
Richard J RomanPhysiology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Fan FanPhysiology, Medical College of Georgia, Augusta University, Augusta, GA, USA. ffan@augusta.edu.ORCID 0000-0003-1463-3610

Funding

TRANSPORT, TRANSFORMATION &REMEDIATION OF VOCS IN THE VADOSE ZONE &GROUND WATERP42ES004699 · UNIVERSITY OF CALIFORNIA DAVIS · 1987 to 2005
$14.0M
UC Davis CounterACT Center of Excellence: Developing Therapeutic Strategies for Mitigating the Chronic Neurological Consequences of Acute Organophosphate IntoxicationU54NS127758 · UNIVERSITY OF CALIFORNIA AT DAVIS · 2025 to 2025
$3.1M
Bioactive lipids as effectors and indicators of the deleterious effects of environmental exposure on chronic diseasesR35ES030443 · UNIVERSITY OF CALIFORNIA AT DAVIS · 2025 to 2025
$1.0M
Adducin, actin cytoskeleton and cognitive impairmentsR01AG057842 · NIA · UNIVERSITY OF MISSISSIPPI MED CTR · PI Jan Michael Williams · 2022 to 2023
$775k
Vascular mechanisms of inhibition of sEH as a novel therapy for AD/ADRDR01AG079336 · UNIVERSITY OF MISSISSIPPI MED CTR · 2025 to 2025
$561k
American Heart Association 25PRE1365157Augusta University TRIBA Faculty Startup FundFoundation for the National Institutes of Health 5P42ES004699Foundation for the National Institutes of Health AG057842Foundation for the National Institutes of Health AG079336Foundation for the National Institutes of Health P20GM104357Foundation for the National Institutes of Health R35ES030443Foundation for the National Institutes of Health U54NS127758Harrington Discovery Institute, University Hospitals A25-1690NIA NIH HHS R01 AG057842NIA NIH HHS R01 AG079336NIA NIH HHS RF1 AG079336NIEHS NIH HHS P42 ES004699NIEHS NIH HHS R35 ES030443NIGMS NIH HHS P20 GM104357NINDS NIH HHS U54 NS127758
6 · The paper itself

Abstract

Alzheimer's Disease and Alzheimer's Disease-related dementias (AD/ADRD) pose major global healthcare challenges, with diabetes mellitus (DM) being a key risk factor. Both AD and DM-related ADRD are characterized by reduced cerebral blood flow, although the exact mechanisms remain unclear. We previously identified compromised cerebral hemodynamics as early signs in TgF344-AD and type 2 DM-ADRD (T2DN) rat models. Genome-wide studies have linked AD/ADRD to SNPs in soluble epoxide hydrolase (sEH). This study explored the effects of sEH inhibition with TPPU on cerebral vascular function and cognition in AD and DM-ADRD models. Chronic TPPU treatment improved cognition in both AD and DM-ADRD rats without affecting body weight. In DM-ADRD rats, TPPU reduced plasma glucose and HbA1c levels. Transcriptomic analysis of primary cerebral vascular smooth muscle cells from AD rats treated with TPPU revealed enhanced pathways related to cell contraction, alongside decreased oxidative stress and inflammation. Both AD and DM-ADRD rats exhibited impaired myogenic responses and autoregulation in the cerebral circulation, which were normalized with chronic sEH inhibition. Additionally, TPPU improved acetylcholine-induced vasodilation in the middle cerebral arteries (MCA) of DM-ADRD rats. Acute TPPU administration unexpectedly caused vasoconstriction in the MCA of DM-ADRD rats at lower doses. In contrast, higher doses or longer durations were required to induce effective vasodilation at physiological perfusion pressure in both control and ADRD rats. Additionally, TPPU decreased reactive oxygen species production in cerebral vessels of AD and DM-ADRD rats. These findings provide novel evidence that chronic sEH inhibition can reverse cerebrovascular dysfunction and cognitive impairments in AD/ADRD, offering a promising avenue for therapeutic development.

Indexed as

Alzheimer DiseaseCerebrovascular CirculationCognitionDiabetes Mellitus, Type 2Epoxide HydrolasesAnimalsDisease Models, AnimalHomeostasisMaleRatsRats, Inbred F344Epoxide HydrolasesAD/ADRDCerebral blood flow autoregulationMyogenic responseOxidative stressSoluble epoxide hydrolaseVascular smooth muscle cells

Identifiers

PMID39903369
PMCPMC12181608

What Socratic holds

Textmetadata
Read underepoch 390

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.