Evidence map›Paper›PMID 40419746›Full record

ArticleNeuroscience bulletin2025

WNK1 Alleviates Chloride Efflux-Induced NLRP3 Inflammasome Activation and Subsequent Neuroinflammation in Early Brain Injury Following Subarachnoid Hemorrhage.

Panpan Zhao, Huimiao Feng, Xinyu Zhou, Jingyuan Zhou, Fangbo Hu, Taotao Hu, Yong Sun

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuroscience bulletin, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
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.

Panpan ZhaoNeurosurgery Department, Institute of Neuroscience, Lianyungang Clinical College of Nanjing Medical University, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, 222000, China.
Huimiao FengJiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China.
Xinyu ZhouDepartment of Neurology, Institute of Neuroscience, Lianyungang Clinical College of Nanjing Medical University, The First Affiliated Hospital of Kangda College of Nanjing Medical University, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People's Hospital of Lianyungang, Lianyungang, 222000, China.
Jingyuan ZhouNeurosurgery Department, Institute of Neuroscience, Lianyungang Clinical College of Nanjing Medical University, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, 222000, China.
Fangbo HuNeurosurgery Department, Institute of Neuroscience, Lianyungang Clinical College of Nanjing Medical University, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, 222000, China.
Taotao HuNeurosurgery Department, Institute of Neuroscience, Lianyungang Clinical College of Nanjing Medical University, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, 222000, China.
Yong SunNeurosurgery Department, Institute of Neuroscience, Lianyungang Clinical College of Nanjing Medical University, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, 222000, China. sunyong@njmu.edu.cn.ORCID http://orcid.org/0009-0008-0281-5875

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage (SAH). WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions, but its role in early brain injury (EBI) after SAH remains unclear. In this study, we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms. WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue, correlating negatively with microglial activation. AAV-WNK1 alleviated brain edema, neuronal necrosis, behavioral deficits, and inflammation by inhibiting NLRP3 inflammasome activation. In hemin-stimulated BV-2 cells, WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines. Chloride counteracted WNK1's inhibitory effects, and WNK1 suppressed P2X7R-induced NLRP3 activation. Mechanistically, WNK1 functioned via the OXSR1/STK39 pathway. These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation, presenting a potential therapeutic target for SAH treatment.

Indexed as

Brain InjuriesChloridesInflammasomesNeuroinflammatory DiseasesNLR Family, Pyrin Domain-Containing 3 ProteinSubarachnoid HemorrhageWNK Lysine-Deficient Protein Kinase 1AnimalsHumansMaleMiceMice, Inbred C57BLMicrogliaProtein Serine-Threonine KinasesRatsRats, Sprague-DawleyChloridesInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinProtein Serine-Threonine KinasesWNK1 protein, humanWnk1 protein, mouseWnk1 protein, ratWNK Lysine-Deficient Protein Kinase 1ChlorideNeuroinflammationNLRP3 inflammasomeP2X7RSubarachnoid hemorrhageWNK1

Identifiers

PMID40419746
PMCPMC12433386

What OpenQuestion holds

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Registered trials

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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.