{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:01:24Z","timestamp":1790258484368,"version":"4.1.0"},"reference-count":164,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Sepsis-associated encephalopathy (SAE) is a serious neurological complication of sepsis that can cause acute cerebral dysfunction and long-term cognitive impairment. Its pathogenesis involves multiple pathological processes, including blood\u2013brain barrier (BBB) disruption, neuroinflammation, microglial and astrocytic responses, oxidative stress, mitochondrial dysfunction, ferroptosis, and pyroptosis. Excessive reactive oxygen species (ROS) production and mitochondrial injury can aggravate cerebrovascular endothelial and BBB damage, promote glial inflammatory responses, and contribute to lipid peroxidation and inflammasome activation, thereby linking neuroinflammation with regulated cell death. Hyperbaric oxygen therapy (HBOT) increases tissue oxygen tension and may exert neuroprotective effects by improving microcirculation and regulating redox homeostasis and inflammatory responses. Available animal studies of SAE suggest that HBOT may attenuate certain aspects of BBB injury and hippocampal neuroinflammation and improve neurobehavioral and cognitive outcomes. Findings from systemic sepsis and other neurological injury models further suggest that antioxidant responses, mitochondrial homeostasis, and signaling pathways associated with ferroptosis and pyroptosis may contribute to these effects. This review summarizes the cellular and molecular processes potentially affected by HBOT within the major pathological mechanisms of SAE and discusses its therapeutic potential and translational challenges based on the available direct and supportive evidence. Current evidence remains predominantly preclinical, and the mechanisms and clinical value of HBOT in SAE require further investigation.<\/jats:p>","DOI":"10.3389\/fncel.2026.1941147","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:21:27Z","timestamp":1790256087000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Hyperbaric oxygen therapy in sepsis-associated encephalopathy: pathophysiological rationale, preclinical evidence, and translational challenges"],"prefix":"10.3389","volume":"20","author":[{"given":"Yikun","family":"Xie","sequence":"first","affiliation":[{"name":"The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital)","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihao","family":"Li","sequence":"additional","affiliation":[{"name":"The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital)","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Li","sequence":"additional","affiliation":[{"name":"The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital)","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital)","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanqi","family":"Song","sequence":"additional","affiliation":[{"name":"The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital)","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Wang","sequence":"additional","affiliation":[{"name":"The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital)","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-endothelial interactions at the blood-brain barrier","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. 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