{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:46Z","timestamp":1792790386272,"version":"4.5.0"},"posted":{"date-parts":[[2025,12,16]]},"group-title":"Neuroscience","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R01AT012312"],"award-info":[{"award-number":["R01AT012312"]}]},{"name":"National Institutes of Health","award":["R01AT011439"],"award-info":[{"award-number":["R01AT011439"]}]},{"name":"National Institutes of Health","award":["U19 NS128613"],"award-info":[{"award-number":["U19 NS128613"]}]},{"name":"the Simons Foundation"},{"name":"Novo Nordisk Foundation","award":["NNF20OC0066419"],"award-info":[{"award-number":["NNF20OC0066419"]}],"id":[{"id":"https:\/\/ror.org\/04txyc737","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the Lundbeck Foundation","award":["R386-2021-165"],"award-info":[{"award-number":["R386-2021-165"]}],"id":[{"id":"https:\/\/ror.org\/03hz8wd80","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Dr. Miriam and Sheldon G. 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Its pathogenesis remains poorly understood because it reflects the combined effects of interacting clinical insults, and because appropriate experimental models for mechanistic studies have been lacking. Delirium most commonly develops in patients undergoing major surgery or requiring intensive care, where inhalational anesthesia, opioid sedation, and mechanical ventilation are common clinical exposures.<\/jats:p>\n                <jats:p>Here, we tested the hypothesis that these clinically relevant interventions are sufficient to induce delirium-like behavior in healthy young wild-type mice by disrupting cerebrospinal fluid (CSF) glymphatic transport. The analysis showed that inhalational anesthesia combined with mechanical ventilation increased intracranial pressure (ICP) and induced a sustained suppression and rerouting of glymphatic waste clearance, resulting in impaired waste clearance, and acute cytokine accumulation.<\/jats:p>\n                <jats:p>These findings identify disruption of brain fluid dynamics as a potential mechanism contributing to delirium in perioperative and intensive care settings. Equally important, this model represents a distinct experimental platform that combines clinically relevant mechanical ventilation, inhalational anesthesia, and opioid analgesia to produce delirium-like behavioral abnormalities in otherwise healthy mice. It therefore provides a powerful tool for future mechanistic studies of delirium pathogenesis.<\/jats:p>","DOI":"10.64898\/2025.12.12.694005","type":"posted-content","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T19:25:14Z","timestamp":1765913114000},"source":"Crossref","is-referenced-by-count":1,"title":["Mechanical Ventilation Impairs Glymphatic Function and Induces Delirium-Like Behavior in Mice"],"prefix":"10.64898","author":[{"given":"Guojun","family":"Liu","sequence":"first","affiliation":[{"name":"Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SiRu","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Brain and Cognitive Sciences, University of Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Newbold","sequence":"additional","affiliation":[{"name":"Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Kroesbergen","sequence":"additional","affiliation":[{"name":"Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungha","family":"Hong","sequence":"additional","affiliation":[{"name":"Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ladr\u00f3n-de-Guevara","sequence":"additional","affiliation":[{"name":"Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Christian Boesen","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Department of Anesthesiology, Zealand University Hospital, 4600, K\u00f8ge, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiken","family":"Nedergaard","sequence":"additional","affiliation":[{"name":"Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, 14642, USA"},{"name":"Center for Translational Neuromedicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Du","sequence":"additional","affiliation":[{"name":"Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester Medical Center, Rochester, NY, 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091713000681000_2025.12.12.694005v2.1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000003299"},{"key":"2026091713000681000_2025.12.12.694005v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-00223-4"},{"key":"2026091713000681000_2025.12.12.694005v2.3","doi-asserted-by":"publisher","DOI":"10.5935\/0103-507X.20170058"},{"key":"2026091713000681000_2025.12.12.694005v2.4","unstructured":"Ren, Y. , et al. 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