Evidence map›Paper›PMID 42405383›Full record

ArticleCNS neuroscience & therapeutics2026

Sympathetic Overactivation Drives Neurogenic Alveolar Epithelial Pyroptosis via the PIEZO2-ER Stress Pathway in Acute Lung Injury Following Intracerebral Hemorrhage.

Shuai Han, Zirui Wang, Qiuyue Zheng, Feng Guo, Yinggang Xiao, Zi Wang, Tianfeng Huang, Yongxin Liang, Bingchun Yan, Ju Gao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in CNS neuroscience & therapeutics, 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. 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

10 authors.

Shuai HanAnesthesiology Department, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University/the First School of Clinical Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.ORCID https://orcid.org/0000-0003-0548-2275
Zirui WangAnesthesiology Department, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University/the First School of Clinical Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Qiuyue ZhengAnesthesiology Department, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University/the First School of Clinical Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Feng GuoAnesthesiology Department, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University/the First School of Clinical Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Yinggang XiaoAnesthesiology Department, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University/the First School of Clinical Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Zi WangAnesthesiology Department, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University/the First School of Clinical Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Tianfeng HuangAnesthesiology Department, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University/the First School of Clinical Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Yongxin LiangPeking University People's Hospital, Qingdao/Women and Children's Hospital, Qingdao University, Qingdao, Shandong, China.
Bingchun YanAnesthesiology Department, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University/the First School of Clinical Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Ju GaoAnesthesiology Department, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou University/the First School of Clinical Medicine, Faculty of Medicine, Yangzhou University, Yangzhou, Jiangsu, China.ORCID https://orcid.org/0009-0008-2715-4233

Funding

the National Natural Science Foundation of China 82172190the National Natural Science Foundation of China 82571398the Research Northern Jiangsu People's Hospital SBGP24005the Research Northern Jiangsu People's Hospital SBJC23005
6 · The paper itself

Abstract

aimsIntracerebral hemorrhage (ICH) frequently triggers acute lung injury (ALI) via sympathetic overactivation. We aimed to investigate the neuroinflammatory mechanisms driving this brain-lung crosstalk and evaluate targeted neuromodulatory interventions via the mechanosensor PIEZO2.

methodsWe utilized an ICH mouse model and norepinephrine (NE)-stimulated MLE12 cells. Pathological mechanisms were explored using transcriptomics, calcium imaging, and Vps35 knockdown. Therapeutic efficacies were assessed via central sympathetic blockade (stellate ganglion block, SGB) and peripheral PIEZO2 inhibition (D-GsMTx4).

resultsNE release exacerbated neurogenic ALI post-ICH. Mechanistically, NE upregulated VPS35, which simultaneously promoted PIEZO2 membrane trafficking and impaired ATP2A2-dependent endoplasmic reticulum (ER) calcium clearance. This induced massive intracellular calcium influx, triggering widespread ER stress and NLRP3/GSDMD-mediated pyroptosis in alveolar epithelial cells. Vps35 knockdown attenuated these effects in vitro. Crucially, targeted interventions with SGB or D-GsMTx4 successfully blocked this lethal central-peripheral cascade, alleviating pulmonary pyroptosis and improving in vivo outcomes.

conclusionSympathetic overactivation drives neurogenic ALI post-ICH via the VPS35/PIEZO2-ER stress-pyroptosis axis. Dual-node neuromodulation (SGB or PIEZO2 inhibition) offers a promising therapeutic strategy for secondary multiorgan complications following acute brain injury.

Indexed as

Acute Lung InjuryAlveolar Epithelial CellsCerebral HemorrhageEndoplasmic Reticulum StressIon ChannelsPyroptosisAnimalsMaleMiceMice, Inbred C57BLNorepinephrineIon ChannelsNorepinephrinePiezo2 protein, mouseacute lung injurybrain‐lung crosstalkintracerebral hemorrhagePIEZO2stellate ganglion blocksympathetic overactivation

Identifiers

PMID42405383
PMCPMC13334374

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LicenceCC BY
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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.