Evidence map›Paper›PMID 31251945›Full record

ArticleNeurochemistry international2019

PARP inhibition in vivo blocks alcohol-induced brain neurodegeneration and neuroinflammatory cytosolic phospholipase A2 elevations.

Dimitrios E Kouzoukas, Jennifer A Schreiber, Nuzhath F Tajuddin, Simon Kaja, Edward J Neafsey, Hee-Yong Kim, Michael A Collins

Open access · greenAbstract read
In one paragraph

Article in Neurochemistry international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.8field-weighted citation impact, top 34% 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

5 citing papers in PubMed, 13 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Dietary Alcohol Consumption Elicits Corneal Toxicity Through the Generation of Cellular Oxidative Stress.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023
    Article
  5. Article
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

7 authors at 2 institutions in 1 country.

Dimitrios E KouzoukasDepartment of Molecular Pharmacology & Therapeutics, Loyola University Chicago, Maywood, IL, USA; Alcohol Research Program, Loyola University Chicago, Maywood, IL, USA; Research Service, Edward Hines Jr. VA Hospital, Hines, IL, USA. Electronic address: dimitrios.kouzoukas@va.gov.
Jennifer A SchreiberNeuroscience Graduate Program, Loyola University Chicago, Maywood, IL, USA; Alcohol Research Program, Loyola University Chicago, Maywood, IL, USA.
Nuzhath F TajuddinDepartment of Molecular Pharmacology & Therapeutics, Loyola University Chicago, Maywood, IL, USA.
Simon KajaDepartment of Molecular Pharmacology & Therapeutics, Loyola University Chicago, Maywood, IL, USA; Neuroscience Graduate Program, Loyola University Chicago, Maywood, IL, USA; Department of Ophthalmology, Loyola University Chicago, Maywood, IL, USA; Alcohol Research Program, Loyola University Chicago, Maywood, IL, USA; Burn Shock Trauma Research Institute, Loyola University Chicago, Maywood, IL, USA; Research Service, Edward Hines Jr. VA Hospital, Hines, IL, USA.
Edward J NeafseyDepartment of Molecular Pharmacology & Therapeutics, Loyola University Chicago, Maywood, IL, USA.
Hee-Yong KimLaboratory of Molecular Signaling, National Institute of Alcoholism and Alcohol Abuse, National Institutes of Health, Bethesda, MD, USA.
Michael A CollinsDepartment of Molecular Pharmacology & Therapeutics, Loyola University Chicago, Maywood, IL, USA; Neuroscience Graduate Program, Loyola University Chicago, Maywood, IL, USA; Alcohol Research Program, Loyola University Chicago, Maywood, IL, USA.
Loyola University Chicago · USNational Institute on Alcohol Abuse and Alcoholism · US

Funding

Alterations In Lipid Metabolism In The Nervous System By EthanolZIAAA000284 · NIAAA · NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM · PI KIM, HEE-YONG · 2009 to 2025
$35.4M
Training in Neuroimmunoendocrine Effects of AlcoholT32AA013527 · NIAAA · LOYOLA UNIVERSITY CHICAGO · PI CHOUDHRY, MASHKOOR A · 2002 to 2021
$4.4M
Binge alcohol-induced neurodegeneration and omega-3 DHA ProtectionU01AA018279 · NIAAA · LOYOLA UNIVERSITY CHICAGO · PI COLLINS, MICHAEL A. · 2009 to 2018
$2.7M
PARP Inhibitor for Improving Functional Recovery After TBI & Binge Alcohol IntoxicationI21RX003170 · VA · EDWARD HINES JR VA HOSPITAL · PI KOUZOUKAS, DIMITRIOS ELIAS · 2019 to 2020
–
NIAAA NIH HHS T32 AA013527NIAAA NIH HHS U01 AA018279RRD VA I21 RX003170
6 · The paper itself

Abstract

Chronic alcoholism promotes brain damage that impairs memory and cognition. High binge alcohol levels in adult rats also cause substantial neurodamage to memory-linked regions, notably, the hippocampus (HC) and entorhinal cortex (ECX). Concurrent with neurodegeneration, alcohol elevates poly (ADP-ribose) polymerase-1 (PARP-1) and cytosolic phospholipase A2 (cPLA2) levels. PARP-1 triggers necrosis when excessively activated, while cPLA2 liberates neuroinflammatory ω-6 arachidonic acid. Inhibitors of PARP exert in vitro neuroprotection while suppressing cPLA2 elevations in alcohol-treated HC-ECX slice cultures. Here, we examined in vivo neuroprotection and cPLA2 suppression by the PARP inhibitor, veliparib, in a recognized adult rat model of alcohol-binging. Adult male rats received Vanilla Ensure containing alcohol (ethanol, 7.1 ± 0.3 g/kg/day), or control (dextrose) ± veliparib (25 mg/kg/day), by gavage 3x daily for 4 days. Rats were sacrificed on the morning after the final binge. HC and ECX neurodegeneration was assessed in fixed sections by Fluoro-Jade B (FJB) staining. Dorsal HC, ventral HC, and ECX cPLA2 levels were quantified by immunoblotting. Like other studies using this model, alcohol binges elevated FJB staining in the HC (dentate gyrus) and ECX, indicating neurodegeneration. Veliparib co-treatment significantly reduced dentate gyrus and ECX neurodegeneration by 79% and 66%, respectively. Alcohol binges increased cPLA2 in the ventral HC by 34% and ECX by 72%, which veliparib co-treatment largely prevented. Dorsal HC cPLA2 levels remained unaffected by alcohol binges, consistent with negligible FJB staining in this brain region. These in vivo results support an emerging key role for PARP in binge alcohol-induced neurodegeneration and cPLA2-related neuroinflammation.

Indexed as

Alcohol-Induced Disorders, Nervous SystemAnimalsBenzimidazolesBinge DrinkingDentate GyrusDisease Models, AnimalEntorhinal CortexEnzyme InductionMaleNerve Tissue ProteinsPhospholipases A2, CytosolicPoly(ADP-ribose) Polymerase InhibitorsRatsRats, Sprague-DawleyBenzimidazolesNerve Tissue ProteinsPhospholipases A2, CytosolicPoly(ADP-ribose) Polymerase InhibitorsveliparibAlcoholCytosolic phospholipase A2NeurodegenerationPoly(ADP-Ribose) polymeraseVeliparib

Identifiers

PMID31251945
PMCPMC6760246
OpenAlexW2956139833

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.