Evidence map›Paper›PMID 32875455›Full record

ArticleTranslational stroke research2021

Deferoxamine Treatment Prevents Post-Stroke Vasoregression and Neurovascular Unit Remodeling Leading to Improved Functional Outcomes in Type 2 Male Diabetic Rats: Role of Endothelial Ferroptosis.

Yasir Abdul, Weiguo Li, Rebecca Ward, Mohammed Abdelsaid, Sherif Hafez, Guangkuo Dong, Sarah Jamil, Victoria Wolf, Maribeth H Johnson, Susan C Fagan and 1 more

Open access · greenAbstract read
In one paragraph

Article in Translational stroke research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
9.2field-weighted citation impact, top 2% 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

75 citing papers in PubMed, 120 citations in OpenAlex.

  1. Danshen (Antioxidants (Basel, Switzerland) · 2026
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15 more citing papers are in PubMed but not listed here.

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

11 authors at 6 institutions in 1 country.

Yasir Abdul *Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
Weiguo Li *Ralph H. Johnson VA Medical Center, Charleston, SC, USA.
Rebecca WardDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Mohammed AbdelsaidSchool of Medicine, Mercer University, Savannah, GA, USA.
Sherif HafezDepartment of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL, USA.
Guangkuo DongDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta, GA, USA.
Sarah JamilRalph H. Johnson VA Medical Center, Charleston, SC, USA.
Victoria WolfRalph H. Johnson VA Medical Center, Charleston, SC, USA.
Maribeth H JohnsonDepartment of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta, GA, USA.
Susan C FaganProgram in Clinical and Experimental Therapeutics, University of Georgia College of Pharmacy, Augusta, GA, USA.
Adviye ErgulRalph H. Johnson VA Medical Center, Charleston, SC, USA. ergul@musc.edu.ORCID http://orcid.org/0000-0003-0873-6015
Medical University of South Carolina · USAugusta University · USGeorgia College & State University · USLarkin University · USMassachusetts General Hospital · USMercer University · US

Funding

Coordinating and Bioinformatics Unit for the MMPC/DiaCompU24DK076169 · NIDDK · AUGUSTA UNIVERSITY · PI MCINDOE, RICHARD A. · 2006 to 2018
$42.4M
TRAINING TO IMPROVE CARDIOVASCULAR THERAPIEST32HL007260 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MENICK, DONALD R. · 1985 to 2021
$11.1M
Vascular Injury and Recovery in Diabetic Ischemic StrokeRF1NS083559 · NINDS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ERGUL, ADVIYE · 2020 to 2022
$2.4M
Progressive Post Stroke Cognitive Impairment:Mechanisms & InterventionR01NS104573 · NINDS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ERGUL, ADVIYE, SHENOY, SOMANATH P RAMMOHAN · 2018 to 2022
$2.3M
Vascular Injury and Recovery in Diabetic Ischemic StrokeR01NS083559 · NINDS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI ERGUL, ADVIYE · 2014 to 2018
$1.9M
Vascular Contributions to Enriched Rehabilitation in HypertensionF32HL158011 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI WOLF, VICTORIA L · 2021 to 2022
$77k
BLR&D Research Career Scientist Award ApplicationIK6BX004471 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI ERGUL, ADVIYE · 2019 to 2025
–
Cerebral Arteriole Structure/Function in Diabetic Ischemic Brain InjuryI01BX000347 · VA · RALPH H JOHNSON VA MEDICAL CENTER · PI ERGUL, ADVIYE · 2009 to 2025
–
BLRD VA I01 BX000347BLRD VA IK6 BX004471Diabetic Complications Research Consortium 17AU3831/18AU3903(DK076169/115255)NHLBI NIH HHS F32 HL158011NHLBI NIH HHS T32 HL007260NIDDK NIH HHS U24 DK076169NIH HHS RF1NS083559NIH HHS RO1 NS104573NIH HHS T32 HL007260NINDS NIH HHS R01 NS083559NINDS NIH HHS R01 NS104573NINDS NIH HHS RF1 NS083559Scientist Development Grant, Amrican Heart Association 16SDG30270013U.S. Department of Veterans Affairs BX000347
6 · The paper itself

Abstract

It is a clinically well-established fact that patients with diabetes have very poor stroke outcomes. Yet, the underlying mechanisms remain largely unknown. Our previous studies showed that male diabetic animals show greater hemorrhagic transformation (HT), profound loss of cerebral vasculature in the recovery period, and poor sensorimotor and cognitive outcomes after ischemic stroke. This study aimed to determine the impact of iron chelation with deferoxamine (DFX) on (1) cerebral vascularization patterns and (2) functional outcomes after stroke in control and diabetic rats. After 8 weeks of type 2 diabetes induced by a combination of high-fat diet and low-dose streptozotocin, male control and diabetic animals were subjected to thromboembolic middle cerebral artery occlusion (MCAO) and randomized to vehicle, DFX, or tPA/DFX and followed for 14 days with behavioral tests. Vascular indices (vascular volume and surface area), neurovascular remodeling (AQP4 polarity), and microglia activation were measured. Brain microvascular endothelial cells (BMVEC) from control and diabetic animals were evaluated for the impact of DFX on ferroptotic cell death. DFX treatment prevented vasoregression and microglia activation while improving AQP4 polarity as well as blood-brain barrier permeability by day 14 in diabetic rats. These pathological changes were associated with improvement of functional outcomes. In control rats, DFX did not have an effect. Iron increased markers of ferroptosis and lipid reactive oxygen species (ROS) to a greater extent in BMVECs from diabetic animals, and this was prevented by DFX. These results strongly suggest that (1) HT impacts post-stroke vascularization patterns and recovery responses in diabetes, (2) treatment of bleeding with iron chelation has differential effects on outcomes in comorbid disease conditions, and (3) iron chelation and possibly inhibition of ferroptosis may provide a novel disease-modifying therapeutic strategy in the prevention of post-stroke cognitive impairment in diabetes.

Indexed as

Diabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2FerroptosisStrokeAnimalsDeferoxamineEndothelial CellsMaleRatsDeferoxamineDiabetesFerroptosisHemorrhagic transformationIron chelationPost-stroke cognitive impairmentStrokeVascularization

Identifiers

PMID32875455
PMCPMC7917163
OpenAlexW3081664061

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.