Evidence map›Paper›PMID 24051278›Full record

ArticleNeurobiology of disease2014

The effect of STAT3 inhibition on status epilepticus and subsequent spontaneous seizures in the pilocarpine model of acquired epilepsy.

H L Grabenstatter, Y Cruz Del Angel, J Carlsen, M F Wempe, A M White, M Cogswell, S J Russek, A R Brooks-Kayal

Open access · greenAbstract read
In one paragraph

Article in Neurobiology of disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% 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

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

  1. Emerging perspectives on mitochondrial dysfunctioning and inflammation in epileptogenesis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021
    Pooled it
  2. Article
  3. Review
  4. Neuroinflammation and Disease: Pathways and Opportunities.Annual review of pharmacology and toxicology · 2026
    Review
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3 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

8 authors at 3 institutions in 1 country.

H L GrabenstatterDepartment of Pediatrics, Division of Neurology and Translational Epilepsy Research Program, University of Colorado School of Medicine, Aurora, CO, USA.
Y Cruz Del AngelDepartment of Pediatrics, Division of Neurology and Translational Epilepsy Research Program, University of Colorado School of Medicine, Aurora, CO, USA.
J CarlsenDepartment of Pediatrics, Division of Neurology and Translational Epilepsy Research Program, University of Colorado School of Medicine, Aurora, CO, USA.
M F WempeDepartment of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
A M WhiteDepartment of Pediatrics, Division of Neurology and Translational Epilepsy Research Program, University of Colorado School of Medicine, Aurora, CO, USA.
M CogswellDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
S J RussekDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA.
A R Brooks-KayalDepartment of Pediatrics, Division of Neurology and Translational Epilepsy Research Program, University of Colorado School of Medicine, Aurora, CO, USA; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Neurology, University of Colorado School of Medicine, Aurora, CO, USA; Children's Hospital Colorado, Aurora, CO, USA. Electronic address: amy.brooks-kayal@childrenscolorado.org.
University of Colorado Denver · USBoston University · USUniversity of Colorado Anschutz Medical Campus · US

Funding

CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025780 · NCRR · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2008 to 2011
$61.3M
Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
GABA(A) Receptor Subunit Regulation in EpileptogenesisR01NS051710 · NINDS · UNIVERSITY OF COLORADO DENVER · PI BROOKS-KAYAL, AMY R., RUSSEK, SHELLEY J · 2006 to 2018
$5.5M
TRAINING IN BIOMOLECULAR PHARMACOLOGYT32GM008541 · NIGMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FARB, DAVID H · 1997 to 2022
$5.2M
NCATS NIH HHS UL1 TR001082NCRR NIH HHS UL1 RR025780NIGMS NIH HHS T32 GM008541NINDS NIH HHS R01 NS051710NINDS NIH HHS R01NS051710
6 · The paper itself

Abstract

Pilocarpine-induced status epilepticus (SE), which results in temporal lobe epilepsy (TLE) in rodents, activates the JAK/STAT pathway. In the current study, we evaluate whether brief exposure to a selective inhibitor of the JAK/STAT pathway (WP1066) early after the onset of SE affects the severity of SE or reduces later spontaneous seizure frequency via inhibition of STAT3-regulated gene transcription. Rats that received systemic WP1066 or vehicle at the onset of SE were continuously video-EEG monitored during SE and for one month to assess seizure frequency over time. Protein and/or mRNA levels for pSTAT3, and STAT3-regulated genes including: ICER, Gabra1, c-myc, mcl-1, cyclin D1, and bcl-xl were evaluated in WP1066 and vehicle-treated rats during stages of epileptogenesis to determine the acute effects of WP1066 administration on SE and chronic epilepsy. WP1066 (two 50mg/kg doses) administered within the first hour after onset of SE results in transient inhibition of pSTAT3 and long-term reduction in spontaneous seizure frequency. WP1066 alters the severity of chronic epilepsy without affecting SE or cell death. Early WP1066 administration reduces known downstream targets of STAT3 transcription 24h after SE including cyclin D1 and mcl-1 levels, known for their roles in cell-cycle progression and cell survival, respectively. These findings uncover a potential effect of the JAK/STAT pathway after brain injury that is physiologically important and may provide a new therapeutic target that can be harnessed for the prevention of epilepsy development and/or progression.

Indexed as

AnimalsBrainCell DeathDentate GyrusDisease Models, AnimalElectroencephalographyHippocampusPhosphorylationPilocarpinePyridinesRatsRats, Sprague-DawleySeizuresSignal TransductionSTAT3 Transcription FactorStatus EpilepticusPilocarpinePyridinesStat3 protein, ratSTAT3 Transcription FactorTyrphostinsWP1066B-cell lymphoma 2B-cell lymphoma-extra largebcl-2bcl-xlcellular regulatory gene that codes for a transcription factorc-mycCyclin D1G1/S-specific cyclin-D1 (encoded by CCND1)ICERinduced myeloid leukemia cell differentiation proteininducible cAMP Early Repressor proteinJAKJanus kinasemcl-1Signal Transducer and Activator of TranscriptionSTATvascular endothelial growth factorVEGF

Identifiers

PMID24051278
PMCPMC3908775
OpenAlexW2087887826

What OpenQuestion holds

Textmetadata
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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.