Evidence map›Paper›PMID 35857628›Full record

ArticleScience translational medicine2022

Enhancing GAT-3 in thalamic astrocytes promotes resilience to brain injury in rodents.

Frances S Cho, Ilia D Vainchtein, Yuliya Voskobiynyk, Allison R Morningstar, Francisco Aparicio, Bryan Higashikubo, Agnieszka Ciesielska, Diede W M Broekaart, Jasper J Anink, Erwin A van Vliet and 5 more

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.5field-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

27 citing papers in PubMed, 46 citations in OpenAlex.

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  14. Astrocyte regional specialization is shaped by postnatal development.bioRxiv : the preprint server for biology · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 5 institutions in 2 countries.

Frances S ChoGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.ORCID 0000-0002-2576-7801
Ilia D VainchteinDepartment of Psychiatry/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0003-3190-8524
Yuliya VoskobiynykGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
Allison R MorningstarGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.ORCID 0000-0002-3857-0450
Francisco AparicioNeuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-3304-9754
Bryan HigashikuboGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
Agnieszka CiesielskaGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.ORCID 0000-0001-6077-3599
Diede W M BroekaartAmsterdam UMC location University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam 1105 AZ, Netherlands.ORCID 0000-0002-4842-0659
Jasper J AninkAmsterdam UMC location University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam 1105 AZ, Netherlands.ORCID 0000-0003-1292-4529
Erwin A van VlietAmsterdam UMC location University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam 1105 AZ, Netherlands.ORCID 0000-0001-5747-3202
Xinzhu YuDepartment of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0003-1244-0110
Baljit S KhakhDepartment of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-0939-1218
Eleonora AronicaAmsterdam UMC location University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam 1105 AZ, Netherlands.ORCID 0000-0002-3542-3770
Anna V MolofskyNeuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.ORCID 0000-0002-4709-2411
Jeanne T PazGladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.ORCID 0000-0001-6339-8130
Gladstone Institutes · USAmsterdam Neuroscience · NLUniversity of California, San Francisco · USUniversity of California, Los Angeles · USNetherlands Institute for Neuroscience · NL

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Ashworth · 1999 to 2026
$209.7M
Fundamental astrocyte biology in intact neural circuitsR35NS111583 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Baljit Khakh · 2019 to 2026
$7.9M
Astrocyte branchlet dysfunction as an early step in brain disordersDP1MH104069 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KHAKH, BALJIT · 2013 to 2017
$3.9M
Coordinate regulation of neural circuit remodeling by glia: a prospective molecular approachDP2MH116507 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MOLOFSKY, ANNA V · 2017 to 2017
$2.4M
The Role of Inflammation in Post-stroke EpileptogenesisR01NS096369 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI PAZ, JEANNE T · 2016 to 2021
$2.3M
Role of Myeloid And CD4+ T Immune Cells in Post-Traumatic PlasticityR01NS121287 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI Jeanne T Paz · 2022 to 2026
$2.2M
EXTRAMULAR RESEARCH FACILITIES CONSTRUCTIONC06RR018928 · NCRR · J. DAVID GLADSTONE INSTITUTES · PI MAHLEY, ROBERT W. · 2003 to 2003
$2.1M
Astrocyte-microglial communication in developmental synapse formationR01MH119349 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MOLOFSKY, ANNA V · 2019 to 2023
$2.0M
Role of Thalamus in Post-stroke epileptogenesisR00NS078118 · NINDS · J. DAVID GLADSTONE INSTITUTES · PI PAZ, JEANNE T · 2014 to 2016
$747k
Determining the role of dysregulated GABA uptake by reactive astrocytes in thalamic circuit hyperexcitability and seizuresF31NS111819 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHO, FRANCES · 2019 to 2020
$75k
NCI NIH HHS P30 CA082103NCRR NIH HHS C06 RR018928NIMH NIH HHS DP1 MH104069NIMH NIH HHS DP2 MH116507NIMH NIH HHS R01 MH119349NINDS NIH HHS F31 NS111819NINDS NIH HHS R00 NS078118NINDS NIH HHS R01 NS096369NINDS NIH HHS R01 NS121287NINDS NIH HHS R35 NS111583
6 · The paper itself

Abstract

Inflammatory processes induced by brain injury are important for recovery; however, when uncontrolled, inflammation can be deleterious, likely explaining why most anti-inflammatory treatments have failed to improve neurological outcomes after brain injury in clinical trials. In the thalamus, chronic activation of glial cells, a proxy of inflammation, has been suggested as an indicator of increased seizure risk and cognitive deficits that develop after cortical injury. Furthermore, lesions in the thalamus, more than other brain regions, have been reported in patients with viral infections associated with neurological deficits, such as SARS-CoV-2. However, the extent to which thalamic inflammation is a driver or by-product of neurological deficits remains unknown. Here, we found that thalamic inflammation in mice was sufficient to phenocopy the cellular and circuit hyperexcitability, enhanced seizure risk, and disruptions in cortical rhythms that develop after cortical injury. In our model, down-regulation of the GABA transporter GAT-3 in thalamic astrocytes mediated this neurological dysfunction. In addition, GAT-3 was decreased in regions of thalamic reactive astrocytes in mouse models of cortical injury. Enhancing GAT-3 in thalamic astrocytes prevented seizure risk, restored cortical states, and was protective against severe chemoconvulsant-induced seizures and mortality in a mouse model of traumatic brain injury, emphasizing the potential of therapeutically targeting this pathway. Together, our results identified a potential therapeutic target for reducing negative outcomes after brain injury.

Indexed as

Brain InjuriesCOVID-19AnimalsAstrocytesDisease Models, AnimalGABA Plasma Membrane Transport ProteinsInflammationMicePolymersRodentiaSARS-CoV-2SeizuresThalamusGABA Plasma Membrane Transport ProteinsGATPolymers

Identifiers

PMID35857628
PMCPMC9491689
OpenAlexW4286247396

What Socratic holds

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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 Socratic graph.