Evidence map›Paper›PMID 26176793›Full record

ArticleNeurobiology of disease2015

Dimethyl fumarate confers neuroprotection by casein kinase 2 phosphorylation of Nrf2 in murine intracerebral hemorrhage.

Loretta O Iniaghe, Paul R Krafft, Damon W Klebe, Eric K I Omogbai, John H Zhang, Jiping Tang

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

Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
5.1field-weighted citation impact, top 5% 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

53 citing papers in PubMed, 78 citations in OpenAlex.

  1. Article
  2. Review
  3. Mitochondrial-targeted therapies in traumatic brain injury: From bench to bedside.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. [Research Progress of Nrf2 and Ferroptosis in Tumor Drug Resistance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023
    Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. The Nrf2 Pathway in Ischemic Stroke: A Review.Molecules (Basel, Switzerland) · 2021
    Review
  19. Review
  20. Potential therapeutic effects of Nrf2 activators on intracranial hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
    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

6 authors at 2 institutions in 2 countries.

Loretta O IniagheDepartment of Physiology and Pharmacology, Loma Linda University, USA; Department of Pharmacology and Toxicology, University of Benin, Nigeria.
Paul R KrafftDepartment of Physiology and Pharmacology, Loma Linda University, USA; Department of Neurosurgery, Loma Linda University, Loma Linda, CA, USA.
Damon W KlebeDepartment of Physiology and Pharmacology, Loma Linda University, USA.
Eric K I OmogbaiDepartment of Pharmacology and Toxicology, University of Benin, Nigeria.
John H ZhangDepartment of Physiology and Pharmacology, Loma Linda University, USA; Department of Anesthesiology, Loma Linda University, Loma Linda, CA, USA.
Jiping TangDepartment of Physiology and Pharmacology, Loma Linda University, USA. Electronic address: jtang@llu.edu.
Loma Linda University · USUniversity of Benin · NG

Funding

Vascular Biology Core FacilityP01NS082184 · NINDS · LOMA LINDA UNIVERSITY · PI PEARCE, WILLIAM J. · 2014 to 2018
$6.1M
NINDS NIH HHS NS082184NINDS NIH HHS P01 NS082184
6 · The paper itself

Abstract

background and purposeEdema formation, inflammation and increased blood-brain barrier permeability contribute to poor outcomes after intracerebral hemorrhage (ICH). This study examined the therapeutic effect of dimethyl fumarate (DMF), a fumaric acid ester that activates nuclear factor erythroid-2 related factor 2 (Nrf2) and Nrf2 heterodimerization effector protein musculo-aponeurotic fibrosarcoma-G (MAFG) in a murine ICH model.

methodsMale CD-1 mice (n=176) were subjected to intrastriatal infusion of bacterial collagenase (n=126), autologous blood (n=18) or sham surgery (n=32). Four (4) animals not subjected to ICH (naive) were also included in the study. After ICH, animals either received vehicle, dimethyl fumarate (10 mg or 100 mg/kg) or casein kinase 2 inhibitor (E)-3-(2,3,4,5-tetrabromophenyl)acrylic acid (TBCA). Thirty-two mice also received scrambled siRNA or MAFG siRNA 24h before ICH. Brain water content and neurological function were evaluated.

resultsDimethyl fumarate reduced Evans blue dye extravasation, decreased brain water content, and improved neurological deficits at 24 and 72 h after ICH. Casein kinase 2 inhibitor TBCA and MAFG siRNA prevented the effect of dimethyl fumarate on brain edema and neurological function. After ICH, ICAM-1 levels increased and casein kinase 2 levels decreased. Dimethyl fumarate reduced ICAM-1 but enhanced casein kinase 2 levels. Again, casein kinase 2 inhibitor TBCA and MAFG siRNA abolished the effect of dimethyl fumarate on ICAM-1 and casein kinase 2. Dimethyl fumarate preserved pNrf2 and MAFG expression in the nuclear lysate after ICH and the effect of dimethyl fumarate was abolished by casein kinase 2 inhibitor TBCA and MAFG siRNA. Dimethyl fumarate reduced microglia activation in peri-hematoma areas after ICH. The protective effect of dimethyl fumarate on brain edema and neurological function was also observed in a blood injection mouse model.

conclusionDimethyl fumarate ameliorated inflammation, reduced blood-brain barrier permeability, and improved neurological outcomes by casein kinase 2 and Nrf2 signaling pathways after experimental ICH in mice.

Indexed as

AcrylatesAnimalsBlood-Brain BarrierBrain EdemaCasein Kinase IICerebral HemorrhageCollagenasesDimethyl FumarateDisease Models, AnimalIntercellular Adhesion Molecule-1MafG Transcription FactorMaleMiceMicrogliaNeuroimmunomodulationNeuroprotective AgentsAcrylatesCasein Kinase IICollagenasesDimethyl Fumarate(E)-3-(2,3,4,5-tetrabromophenyl)acrylic acidIcam1 protein, mouseIntercellular Adhesion Molecule-1Mafg protein, mouseMafG Transcription FactorNeuroprotective AgentsNfe2l2 protein, mouseNF-E2-Related Factor 2Protein Kinase InhibitorsRepressor ProteinsCasein kinase 2Dimethyl fumarateEvans Blue extravasationInflammationIntracerebral hemorrhageMusculo-aponeurotic fibrosarcoma-GPhosphorylated nuclear factor erythroid-2 related factor 2 (Nrf2)

Identifiers

PMID26176793
PMCPMC4640980
OpenAlexW1157059961

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.