Evidence map›Paper›PMID 42053428›Full record

ArticleCNS neuroscience & therapeutics2026

HBO-PC Reprograms Neuroimmune Metabolism Through Disruption of the LRG1-HIF-1α-IL-6-STAT3 Amplification Loop Attenuates Pyroptosis and Ischemia-Reperfusion Injury.

Wenying Lv, Junzhe Lv, Kexin Xiong, Shunshun Yuan, Jingyao Yang, Dazhi Guo

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Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Wenying LvDepartment of Hyperbaric Oxygen, The Sixth Medical Center, PLA General Hospital, Beijing, China.
Junzhe LvDepartment of Hyperbaric Oxygen, The Sixth Medical Center, PLA General Hospital, Beijing, China.
Kexin XiongDepartment of Hyperbaric Oxygen, The Sixth Medical Center, PLA General Hospital, Beijing, China.
Shunshun YuanDepartment of Hyperbaric Oxygen, The Sixth Medical Center, PLA General Hospital, Beijing, China.
Jingyao YangDepartment of Hyperbaric Oxygen, The Sixth Medical Center, PLA General Hospital, Beijing, China.
Dazhi GuoDepartment of Hyperbaric Oxygen, The Sixth Medical Center, PLA General Hospital, Beijing, China.ORCID https://orcid.org/0000-0002-9910-9625

Funding

National Key Research and Development Program of China 2022YFA1104300
6 · The paper itself

Abstract

backgroundNeuroinflammation and pyroptosis driven by excessive microglial activation play key roles in cerebral ischemia-reperfusion injury (CIRI). Hyperbaric oxygen preconditioning (HBO-PC) exhibits neuroprotective effects, but its mechanisms remain unclear. Leucine-rich α-2-glycoprotein 1 (LRG1) is implicated in CIRI pathology, yet whether HBO-PC modulates neuroinflammation and pyroptosis via LRG1 is unknown.

methodsA mouse CIRI model was generated by middle cerebral artery occlusion. HBO-PC and LRG1 siRNA knockdown were applied. Neurological function and molecular changes were evaluated.

resultsHBO-PC reduced infarct volume and improved neurological outcomes, while downregulating LRG1 in neurons and microglia. LRG1 promoted HIF-1α accumulation by inhibiting prolyl hydroxylase activity, leading to caspase-3-dependent GSDME cleavage and pyroptosis. Released IL-6 activated STAT3, which further transcriptionally upregulated LRG1, forming a self-amplifying HIF-1α/GSDME/IL-6/STAT3 loop. HBO-PC disrupted this circuit and shifted microglia toward an anti-inflammatory phenotype.

conclusionHBO-PC protects against CIRI by breaking the LRG1-HIF-1α-IL-6-STAT3 feedback loop, thereby attenuating pyroptosis and neuroinflammation while promoting anti-inflammatory microglial polarization. LRG1 represents a promising therapeutic target in ischemic brain injury.

Indexed as

GlycoproteinsHypoxia-Inducible Factor 1, alpha SubunitInterleukin-6Ischemic PreconditioningNeuroimmunomodulationPyroptosisReperfusion InjuryAnimalsInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLSTAT3 Transcription FactorGlycoproteinsHif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitInterleukin-6LRG1 protein, mouseStat3 protein, mouseSTAT3 Transcription FactorCIRIGSDMEHBO‐PCLRG1pyroptosis

Identifiers

PMID42053428
PMCPMC13127231

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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.