{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:02:00Z","timestamp":1790146920227,"version":"4.0.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oxidative stress and neuroinflammation constitute key pathological contributors to high-altitude cerebral edema (HACE). Carnosic acid (CA) exerts important roles in neurodegeneration and brain injury, but its function in HACE remains elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>High-altitude hypobaric hypoxic (HH)-mimicked HACE rats were administered carnosic acid. The effects on hematological parameter changes, blood\u2013brain barrier (BBB) permeability, energetic metabolism disorder, cognitive and motor impairment, oxidative stress, and microglia-mediated neuroinflammation were explored. The function of carnosic acid in microglia-mediated damage to astrocytes and endothelial cells under hypoxia was investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Carnosic acid dose-dependently normalized aberrant hematological parameter changes, brain water content, and histopathological changes in HH-mimicked HACE rats. Moreover, HH conditions enhanced BBB permeability and BBB-related aquaporin 4 (AQP4) expression and decreased BBB-related occludin and zonula occludens-1 (ZO-1) expression, which were reversed after carnosic acid. Carnosic acid alleviated energetic metabolism disorder and improved cognitive and motor impairment in HACE rats. Carnosic acid attenuated HH-evoked oxidative stress by inhibiting reactive oxygen species (ROS) and malondialdehyde levels and increased antioxidant glutathione and superoxide dismutase levels. Carnosic acid suppressed HH-induced microglia activation and pro-inflammatory response. Additionally, aberrant activation of the NF-\u03baB\u2013NLRP3 inflammasome axis in HACE rats was also inhibited by carnosic acid. Carnosic acid inhibited hypoxia-induced pro-inflammatory microglia activation by the NF-\u03baB\u2013NLRP3 pathway. Moreover, carnosic acid also attenuated hypoxia-activated microglia-induced AQP4 expression in astrocytes and damage to the endothelial tight junction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Carnosic acid may attenuate the pathological progression of HACE by restraining oxidative stress and microglia activation-induced neuroinflammation via the NF-\u03baB\u2013NLRP3 axis, supporting it as a promising neuroprotective intervention for HACE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1892158","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:20:55Z","timestamp":1790144455000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Carnosic acid alleviates high-altitude cerebral edema by suppressing oxidative stress and microglia activation-induced neuroinflammation"],"prefix":"10.3389","volume":"17","author":[{"given":"Junlan","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Second Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningwei","family":"Che","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Second Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Second Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"11663","DOI":"10.1007\/s11356-020-07736-1","article-title":"Carnosic acid alleviates chlorpyrifos-induced oxidative stress and inflammation in mice cerebral and ocular tissues","volume":"27","author":"AlKahtane","year":"2020","journal-title":"Environ. 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