Evidence map›Paper›PMID 40096965›Full record

ArticleStroke and vascular neurology2025

LRRC8A in endothelial cells contributes to the aberrant blood-brain barrier integrity in ischaemic stroke.

Yanfei Tian, Yan Wang, Yupeng Zhao, Chang Liu, Xiaoyu Zhang, Yan Zhang, Zhenghui Wu, Yue Kong, Bo Wang, Huaxing Zhang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stroke and vascular neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. 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

13 authors.

Yanfei Tian *Department of Pharmacology, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China.
Yan Wang *Department of Pharmacology, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China.
Yupeng ZhaoDepartment of Pharmacology, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China.
Chang LiuDepartment of Pharmacology, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China.
Xiaoyu ZhangCore Facilities and Centers, Hebei Medical University, Shijiazhuang, Hebei, China.
Yan ZhangDepartment of Pharmacology, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China.
Zhenghui WuDepartment of Pharmacology, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China.
Yue KongDepartment of Pharmacology, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China.
Bo WangDepartment of Pharmacology, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China.
Huaxing ZhangCore Facilities and Centers, Hebei Medical University, Shijiazhuang, Hebei, China.
Xiaona DuDepartment of Pharmacology, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China.
Hailin ZhangDepartment of Pharmacology, The Key Laboratory of New Drug Pharmacology and Toxicology, Hebei Medical University, Shijiazhuang, Hebei, China zhanghr@hebmu.edu.cn zhanghl@hebmu.edu.cn.
Huiran ZhangThe Key Laboratory of Neural and Vascular Biology; Ministry of Education, Shijiazhuang, China zhanghr@hebmu.edu.cn zhanghl@hebmu.edu.cn.ORCID http://orcid.org/0000-0001-8105-2715

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe increased permeability of the blood-brain barrier (BBB) is a critical contributor to the high mortality following ischaemic stroke. However, the mechanisms regulating BBB integrity remain poorly understood. Leucine-rich repeat-containing 8A (LRRC8A) is a chloride channel critical for cellular volume homeostasis and plays a key role in regulating neuronal injury during ischaemia. However, its impact on BBB function is currently unclear.

methodsA transient middle cerebral artery occlusion model was established to investigate the impact of LRRC8A on BBB integrity. Laser speckle contrast imaging was used to monitor cortical blood flow. Primary mouse and human brain microvascular endothelial cells (m/hBMVECs) were subjected to oxygen-glucose deprivation (OGD) and re-oxygenation for varying durations. Patch-clamp recordings were performed to measure volume-regulated chloride currents. Immunostaining was conducted to evaluate protein expression. Cell permeability was evaluated with transwell assay.

resultsLRRC8A deletion in endothelial cells ameliorates the infarct area and mitigates BBB leakage. Ischaemia dramatically upregulates the expression of LRRC8A in endothelial cells, concurrently downregulating tight junction proteins. OGD exposure augments the VRCC current mediated by LRRC8A in BMVECs. In contrast, inhibiting LRRC8A promotes the expression of ZO-1 and VE-cadherin, thereby preserving the integrity of endothelial cells. With-no-lysine kinase 1 (WNK1) inhibition contributes to LRRC8A-induced BBB damage post-ischaemic stroke. Eupatorin, a newly identified LRRC8A inhibitor, exerts neuroprotective effects against ischaemic stroke.

conclusionsLRRC8A in BMVECs plays a pivotal role in modulating BBB integrity, a process regulated by WNK1. As an LRRC8A inhibitor, Eupatorin holds the potential for ischaemic stroke therapy.

Indexed as

Blood-Brain BarrierCapillary PermeabilityEndothelial CellsInfarction, Middle Cerebral ArteryIschemic StrokeMembrane ProteinsAnimalsCadherinsCell HypoxiaCells, CulturedDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLMice, KnockoutCadherinsMembrane ProteinsZonula Occludens-1 ProteinCerebral InfarctionIschaemic Stroke

Identifiers

PMID40096965
PMCPMC12573346

What Socratic holds

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LicenceCC BY-NC
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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.