{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:09:30Z","timestamp":1791839370100,"version":"4.3.4"},"reference-count":137,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bio and Medical Technology Development Program of the National Research Foundation","award":["NRF-2023R1A2C100531"],"award-info":[{"award-number":["NRF-2023R1A2C100531"]}]},{"name":"Patient-Centered Clinical Research Coordinating Center","award":["RS-2024-00439915"],"award-info":[{"award-number":["RS-2024-00439915"]}]},{"name":"The Catholic Medical Center Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Subarachnoid hemorrhage (SAH), often resulting from aneurysmal rupture, remains a life-threatening cerebrovascular disorder with high morbidity and mortality. While previous research has focused primarily on cerebral damage and neurological outcomes, growing evidence suggests that SAH also causes systemic complications, including pulmonary dysfunction. The underlying mechanisms linking SAH to lung injury, however, are not fully understood. The glymphatic system, a perivascular network that facilitates the clearance of cerebrospinal fluid (CSF) and interstitial waste from the brain, plays a critical role in maintaining central nervous system (CNS) homeostasis. Aquaporin-4 (AQP4) water channels, predominantly expressed in astrocytic end feet, are essential for efficient glymphatic flow. Emerging studies have shown that SAH impairs glymphatic function by disrupting AQP4 polarity and CSF circulation, resulting in the accumulation of neurotoxic substances and neuroinflammation. Recent findings further suggest that glymphatic dysfunction may exert systemic effects beyond the CNS, contributing to a breakdown of the brain\u2013lung axis. The release of pro-inflammatory cytokines, blood degradation products, and damage-associated molecular patterns (DAMPs) into systemic circulation can promote pulmonary endothelial injury and trigger immune responses in the lungs. This phenomenon is exacerbated by impaired clearance via the glymphatic system, amplifying systemic inflammation and increasing the risk of acute lung injury (ALI) or neurogenic pulmonary edema (NPE). This review proposes a novel perspective linking glymphatic impairment with pulmonary complications after SAH. Understanding this connection could open new therapeutic avenues\u2014such as targeting AQP4 function, enhancing CSF circulation, or modulating the inflammatory response\u2014to mitigate both neurological and respiratory sequelae in SAH patients.<\/jats:p>","DOI":"10.3390\/cells14211739","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T16:09:47Z","timestamp":1762358987000},"page":"1739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Glymphatic Dysfunction in Neuro-Pulmonary Complications Following Subarachnoid Hemorrhage: A New Perspective on Brain\u2013Lung Axis Disruption"],"prefix":"10.3390","volume":"14","author":[{"given":"Eun Chae","family":"Lee","sequence":"first","affiliation":[{"name":"Medical Life Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Sang","family":"Oh","sequence":"additional","affiliation":[{"name":"Medical Life Science, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"},{"name":"Department of Neurosurgery, Uijeongbu St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S0140-6736(16)30668-7","article-title":"Spontaneous subarachnoid haemorrhage","volume":"389","author":"Macdonald","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/B978-0-444-63600-3.00012-X","article-title":"Management of aneurysmal subarachnoid hemorrhage","volume":"140","author":"Etminan","year":"2017","journal-title":"Handb. 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