Evidence map›Paper›PMID 42325092›Full record

ArticleJCI insight2026

Microglial SWELL1 deficiency drives male-specific seizure vulnerability but paradoxical neuroprotection through impaired phagocytosis.

Abhijeet S Barath, Aastha Dheer, Laura Montier, Mekenzie M Peshoff, Emily Dale, Flavia Goche, Thanh Thanh Le Nguyen, Mastura Akter, FangFang Qi, Dimitrios Kleidonas and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Abhijeet S BarathDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Aastha DheerDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Laura MontierCenter for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Mekenzie M PeshoffCenter for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Emily DaleDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Flavia GocheDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Thanh Thanh Le NguyenDepartment of Genetics, Yale School of Medicine, New Haven, Connecticut, USA.
Mastura AkterCenter for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
FangFang QiDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Dimitrios KleidonasCenter for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Lauren HarrisCenter for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Sarah A JewaneeCenter for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Rongzhuo Hua *Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Tejaswani DatlaCenter for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Anthony D UmpierreDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Dale B BoscoDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Koichiro HaruwakaCenter for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Rajan SahDepartment of Internal Medicine, Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri, USA.
Long-Jun WuDepartment of Neurology, Mayo Clinic, Rochester, Minnesota, USA.

Funding

The Role of Microglia in EpilepsyR01NS088627 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI WU, LONG-JUN · 2014 to 2023
$3.6M
How microglia sense and regulate neuronal activity in the adult brainR35NS132326 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Long-Jun Wu · 2023 to 2026
$3.2M
SWELL1-LRRC8 mediated regulation of skeletal muscle function and metabolismR01DK127080 · NIDDK · WASHINGTON UNIVERSITY · PI SAH, RAJAN · 2021 to 2024
$1.7M
Understanding the role of triggering receptor expressed on myeloid cells 2 (TREM2) on microglia and macrophages in gliomasF31NS141605 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Mekenzie Peshoff · 2025 to 2026
$76k
NIDDK NIH HHS R01 DK127080NINDS NIH HHS F31 NS141605NINDS NIH HHS R01 NS088627NINDS NIH HHS R35 NS132326
6 · The paper itself

Abstract

The discovery of genes encoding the volume-regulated anion channel (VRAC) has enabled detailed exploration of its cell type-specific roles in the brain. LRRC8A (SWELL1) is the essential VRAC subunit. We observed seizure-induced, subunit-specific changes in microglial VRAC expression and investigated its function using conditional KO (cKO) of LRRC8A in microglia. SWELL1 cKO mice exhibited a male-specific increase in kainate-induced seizure severity, yet showed paradoxical neuroprotection against seizure-associated neuronal loss. Mechanistically, SWELL1 deletion led to a cell-autonomous reduction in microglial density and decreased release of VRAC-permeable neuroactive metabolites, including taurine, GABA, and glutamate in culture. Additionally, impaired phagocytic kinetics and reduced lysosomal biogenesis contributed to the observed neuroprotection. These findings reveal potentially novel roles for microglial VRAC in regulating seizure outcomes and microglia-neuron interactions.

Indexed as

Membrane ProteinsMicrogliaNeuroprotectionPhagocytosisSeizuresAnimalsDisease Models, AnimalKainic AcidMaleMiceMice, KnockoutNeuronsKainic AcidLRRC8A protein, mouseMembrane ProteinsEpilepsyImmunologyNeuroscienceSeizures

Identifiers

PMID42325092
PMCPMC13313489

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.