Evidence map›Paper›PMID 42867612›Full record

ArticleGeroScience2026

Inhibition of soluble epoxide hydrolase rescues cognitive deficits by preserving neurovascular integrity and attenuating glial and neuropathology in diabetic-related dementia.

Xing Fang, Jane J Border, Huawei Zhang, Gilbert C Morgan, Andrew Gregory, Yvan Hanscom-Trofy, Rui Dong, Jun Yang, Sung Hee Hwang, Christophe Morisseau and 3 more

Abstract read
PubMed Publisher
In one paragraph

Article in GeroScience, 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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

13 authors.

Xing FangDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
Jane J BorderDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
Huawei ZhangDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA.
Gilbert C MorganDepartment of Physiology, Medical College of Georgia, Augusta University, 1462 Laney Walker Blvd, Augusta, GA, 30912, USA.
Andrew GregoryDepartment of Physiology, Medical College of Georgia, Augusta University, 1462 Laney Walker Blvd, Augusta, GA, 30912, USA.
Yvan Hanscom-TrofyDepartment of Physiology, Medical College of Georgia, Augusta University, 1462 Laney Walker Blvd, Augusta, GA, 30912, USA.
Rui DongDepartment of Physiology, Medical College of Georgia, Augusta University, 1462 Laney Walker Blvd, Augusta, GA, 30912, USA.
Jun YangEntomology and Nematology, UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, USA.
Sung Hee HwangEntomology and Nematology, UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, USA.
Christophe MorisseauEntomology and Nematology, UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, USA.
Bruce D HammockEntomology and Nematology, UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, USA.
Fan FanDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA. ffan@augusta.edu.ORCID http://orcid.org/0000-0003-1463-3610
Richard J RomanDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA. rroman@umc.edu.ORCID http://orcid.org/0000-0002-5581-0217

Funding

UC Davis CounterACT Center of Excellence: Developing Therapeutic Strategies for Mitigating the Chronic Neurological Consequences of Acute Organophosphate IntoxicationU54NS127758 · NINDS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Amy R. Brooks-Kayal, Pamela J Lein · 2022 to 2026
$17.2M
Supplement for bioactive lipids as effectors and indicators of the deleterious effects of human healthR35ES030443 · NIEHS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI MORISSEAU, CHRISTOPHE HP · 2019 to 2025
$5.8M
American Heart Association 25POST1363814American Heart Association 25PRE1365157Augusta University TRIBA/ Physiology Faculty Startup FundHarrington Discovery Institute, University Hospitals A25-1690NIA NIH HHS AG057842NIA NIH HHS AG094068NIEHS NIH HHS R35ES030443NIH AG079336NINDS NIH HHS U54NS127758
6 · The paper itself

Abstract

Diabetes mellitus (DM) is a major risk factor contributing to the development of Alzheimer's disease-related dementias (ADRD). While one of the early symptoms of both Alzheimer's disease (AD) and DM-related ADRD is a reduction in cerebral blood flow, the underlying biological mechanisms driving this decline remain to be fully elucidated. Genome-wide association studies have linked AD/ADRD to single-nucleotide polymorphisms in the gene encoding soluble epoxide hydrolase (sEH), an enzyme we previously reported to be upregulated in the brains of an AD rat model. Our previous studies also demonstrated that chronic sEH inhibition with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) preserves hippocampal-dependent spatial learning and memory and improves cerebral hemodynamics in both AD and DM-ADRD models. In the present study, we found that chronic TPPU treatment (1 mg/kg/day) reduced sEH expression in the brain, improved cortical-based non-spatial recognition memory involving both cortical and hippocampal networks, and reduced anxiety in DM-ADRD rats. TPPU improved brain perfusion and normalized impaired whisker-evoked functional hyperemia, an effect associated with increased Kir2.1 expression and neurovascular coupling in cerebral capillaries. Furthermore, TPPU increased tight junction protein expression (ZO-1 and OCLN), mitigated capillary rarefaction, and suppressed astrocyte and microglial activation in DM-ADRD rats. At the cellular level, TPPU attenuated hippocampal neurodegeneration, restored the expression of synaptic proteins (PSD95 and SY38), and reduced levels of proinflammatory chemokines, including MCP-1, RANTES, and MIP-1α, in the hippocampus of DM-ADRD rats. In conclusion, TPPU preserves cognitive function in DM-ADRD by mitigating cerebrovascular dysfunction, neuroinflammation and gliosis, thereby preserving synaptic integrity and neuronal survival, and represents a promising therapeutic strategy for DM-ADRD.

Indexed as

Blood–brain barrierCapillary rarefactionDiabetic-related dementiaNeuroinflammationNeurovascular couplingSoluble epoxide hydrolase

Identifiers

PMID42867612

What OpenQuestion holds

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Registered trials

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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.