{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T14:14:02Z","timestamp":1779804842199,"version":"3.53.1"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1104300"],"award-info":[{"award-number":["2022YFA1104300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Neuroinflammation and pyroptosis driven by excessive microglial activation play key roles in cerebral ischemia\u2013reperfusion injury (CIRI). Hyperbaric oxygen preconditioning (HBO\u2010PC) exhibits neuroprotective effects, but its mechanisms remain unclear. Leucine\u2010rich \u03b1\u20102\u2010glycoprotein 1 (LRG1) is implicated in CIRI pathology, yet whether HBO\u2010PC modulates neuroinflammation and pyroptosis via LRG1 is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A mouse CIRI model was generated by middle cerebral artery occlusion. HBO\u2010PC and LRG1 siRNA knockdown were applied. Neurological function and molecular changes were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HBO\u2010PC reduced infarct volume and improved neurological outcomes, while downregulating LRG1 in neurons and microglia. LRG1 promoted HIF\u20101\u03b1 accumulation by inhibiting prolyl hydroxylase activity, leading to caspase\u20103\u2010dependent GSDME cleavage and pyroptosis. Released IL\u20106 activated STAT3, which further transcriptionally upregulated LRG1, forming a self\u2010amplifying HIF\u20101\u03b1\/GSDME\/IL\u20106\/STAT3 loop. HBO\u2010PC disrupted this circuit and shifted microglia toward an anti\u2010inflammatory phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HBO\u2010PC protects against CIRI by breaking the LRG1\u2013HIF\u20101\u03b1\u2013IL\u20106\u2013STAT3 feedback loop, thereby attenuating pyroptosis and neuroinflammation while promoting anti\u2010inflammatory microglial polarization. LRG1 represents a promising therapeutic target in ischemic brain injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70907","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:52:41Z","timestamp":1777470761000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>HBO<\/scp>\n                    \u2010\n                    <scp>PC<\/scp>\n                    Reprograms Neuroimmune Metabolism Through Disruption of the\n                    <scp>LRG1<\/scp>\n                    \u2010\n                    <scp>HIF<\/scp>\n                    \u20101\u03b1\u2010\n                    <scp>IL<\/scp>\n                    \u20106\u2010\n                    <scp>STAT3<\/scp>\n                    Amplification Loop Attenuates Pyroptosis and Ischemia\u2013Reperfusion Injury"],"prefix":"10.1002","volume":"32","author":[{"given":"Wenying","family":"Lv","sequence":"first","affiliation":[{"name":"Department of Hyperbaric Oxygen The Sixth Medical Center, PLA General Hospital  Beijing China"},{"name":"The Second School of Clinical Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzhe","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Hyperbaric Oxygen The Sixth Medical Center, PLA General Hospital  Beijing China"},{"name":"Medical School of Chinese PLA  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Hyperbaric Oxygen The Sixth Medical Center, PLA General Hospital  Beijing China"},{"name":"School of Medicine South China University of Technology  Guangzhou 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