{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T06:26:07Z","timestamp":1772000767745,"version":"3.50.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"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>\n                    Neurologic injury remains a critical complication of deep hypothermic circulatory arrest (DHCA) in aortic arch surgery, with neuroinflammation driven by multiple factors in its pathogenesis. While circular RNAs (circRNAs) are known to modulate inflammatory responses, their specific role in DHCA-associated brain injury has not been established. In this study, we demonstrated that circFRRS1 exacerbates hippocampal neuroinflammation via the miR-27a-3p\/TLR4 axis through integrated\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    approaches. In a rat model of DHCA, machine learning-based motion sequencing (MoSeq) identified delirium-like behaviors, accompanied by hippocampal neuronal necrosis and activation of NLRP3 inflammasome. circFRRS1 was significantly upregulated in hippocampal tissue following DHCA and in hypoxic-ischemic PC-12 cells. Silencing circFRRS1 attenuated oxygen-glucose deprivation\/reperfusion (OGD\/R)-induced cytotoxicity and suppressed the TLR4\/NF-\u03baB\/NLRP3 signaling pathway. Mechanistically, circFRRS1 acts as a molecular sponge for miR-27a-3p, thereby relieving its repression of TLR4; inhibition of miR-27a-3p abolished the observed neuroprotective effects. This study identifies circFRRS1 as the first reported circRNA to regulate DHCA-induced neuroinflammation, uncovering a novel epigenetic mechanism and suggesting the potential of circRNA-targeted therapies as adjuvants to conventional hypothermic strategies.\n                  <\/jats:p>","DOI":"10.3389\/fncel.2026.1750887","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T05:32:48Z","timestamp":1771997568000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["CircFRRS1 drives neuroinflammation through the miR-27a-3p\/TLR4 pathway after deep hypothermic circulatory arrest"],"prefix":"10.3389","volume":"20","author":[{"given":"Weidong","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianlong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiopulmonary Bypass, National Center for Cardiovascular Disease and Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Songjiang Research Institute, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiopulmonary Bypass, National Center for Cardiovascular Disease and Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiopulmonary Bypass, National Center for Cardiovascular Disease and Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiopulmonary Bypass, National Center for Cardiovascular Disease and Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziyu","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingyang","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Cardiopulmonary Bypass, National Center for Cardiovascular Disease and Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changwei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1447007","DOI":"10.3389\/fcvm.2024.1447007","article-title":"Temperature management in acute type A aortic dissection treatment: Deep vs. moderate hypothermic circulatory arrest. 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