Evidence map›Paper›PMID 21853027›Full record

ArticlePloS one2011

Targeted over-expression of glutamate transporter 1 (GLT-1) reduces ischemic brain injury in a rat model of stroke.

Brandon K Harvey, Mikko Airavaara, Jason Hinzman, Emily M Wires, Matthew J Chiocco, Douglas B Howard, Hui Shen, Greg Gerhardt, Barry J Hoffer, Yun Wang

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

71 citing papers in PubMed, 108 citations in OpenAlex.

  1. Review
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  5. The Role of Nanotechnology in Understanding the Pathophysiology of Traumatic Brain Injury.Central nervous system agents in medicinal chemistry · 2025
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11 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

10 authors at 3 institutions in 1 country.

Brandon K HarveyIntramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, United States of America. bharvey@mail.nih.gov
Mikko Airavaara
Jason Hinzman
Emily M Wires
Matthew J Chiocco
Douglas B Howard
Hui Shen
Greg Gerhardt
Barry J Hoffer
Yun Wang
National Institutes of Health · USNational Institute on Drug Abuse · USUniversity of Kentucky · US

Funding

Optogenetics and Transgenic Technology CoreZICDA000555 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI HARVEY, BRANDON · 2009 to 2017
$10.0M
Gene Therapy And NeurodegenerationZIADA000443 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI HARVEY, BRANDON · 2009 to 2020
$2.7M
Neuroprotective and neuroregenerative effects of trophic factorsZIADA000429 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI WANG, YUN · 2009 to 2013
$2.4M
Neuroprotective/regenerative effects of small molecules and trophic factorsZIADA000461 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI WANG, YUN · 2009 to 2013
$2.3M
Neurochem Chip: Methodology to Study Untethered RatsR01DA017186 · NIDA · UNIVERSITY OF KENTUCKY · PI GERHARDT, GREG A. · 2003 to 2007
$2.0M
Effects of over-expression of u-opioid receptor on methamphetamine-sensitizationZIADA000576 · NIDA · NATIONAL INSTITUTE ON DRUG ABUSE · PI WANG, YUN · 2011 to 2013
$557k
Alterations in Glutamate Neurotransmission after Experimental Brain InjuryF31NS067899 · NINDS · UNIVERSITY OF KENTUCKY · PI HINZMAN, JASON MICHAEL · 2010 to 2011
$65k
Intramural NIH HHSNIDA NIH HHS DA017186NIDA NIH HHS R01 DA017186NINDS NIH HHS F31 NS067899NINDS NIH HHS F31NS067899
6 · The paper itself

Abstract

Following the onset of an ischemic brain injury, the excitatory neurotransmitter glutamate is released. The excitotoxic effects of glutamate are a major contributor to the pathogenesis of a stroke. The aim of this study was to examine if overexpression of a glutamate transporter (GLT-1) reduces ischemic brain injury in a rat model of stroke. We generated an adeno-associated viral (AAV) vector expressing the rat GLT-1 cDNA (AAV-GLT1). Functional expression of AAV-GLT1 was confirmed by increased glutamate clearance rate in non-stroke rat brain as measured by in vivo amperometry. AAV-GLT1 was injected into future cortical region of infarction 3 weeks prior to 60 min middle cerebral artery occlusion (MCAo). Tissue damage was assessed at one and two days after MCAo using TUNEL and TTC staining, respectively. Behavioral testing was performed at 2, 8 and 14 days post-stroke. Animals receiving AAV-GLT1, compared to AAV-GFP, showed significant decreases in the duration and magnitude of extracellular glutamate, measured by microdialysis, during the 60 minute MCAo. A significant reduction in brain infarction and DNA fragmentation was observed in the region of AAV-GLT1 injection. Animals that received AAV-GLT1 showed significant improvement in behavioral recovery following stroke compared to the AAV-GFP group. We demonstrate that focal overexpression of the glutamate transporter, GLT-1, significantly reduces ischemia-induced glutamate overflow, decreases cell death and improves behavioral recovery. These data further support the role of glutamate in the pathogenesis of ischemic damage in brain and demonstrate that targeted gene delivery to decrease the ischemia-induced glutamate overflow reduces the cellular and behavioral deficits caused by stroke.

Indexed as

Amino Acid Transport System X-AGAnimalsBehavior, AnimalBrain InfarctionBrain InjuriesBrain IschemiaCerebral CortexDependovirusDisease Models, AnimalGene Expression RegulationGlutamatesHEK293 CellsHumansInfarction, Middle Cerebral ArteryIn Situ Nick-End LabelingMaleAmino Acid Transport System X-AGGlutamates

Identifiers

PMID21853027
PMCPMC3154194
OpenAlexW1966610248

What OpenQuestion holds

Textmetadata
LicenceCC0
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.