{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:07:19Z","timestamp":1791360439813,"version":"4.3.1"},"reference-count":253,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy Carol Davila"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Brain function is reliant upon maintaining a constant internal environment; however, the methods employed to maintain this environment have historically been viewed as largely passive in nature, relying on diffusion and vascular pulsations to create the conditions necessary for continued brain activity. This review seeks to provide an overview of current data suggesting that brain clearance is in fact an active process that is dependent upon both the current regulatory state of the brain and the presence of noradrenergic slow vasomotion, which is generated by rhythmic output from the locus coeruleus (LC). The LC-generated output has been found to influence the degree of contraction exhibited by pericytes, the geometric shape of astrocytic end-feet, and vascular tone, ultimately impacting the rate of exchange between cerebrospinal fluid (CSF), interstitial fluid (ISF), and the blood\u2013brain barrier through aquaporin-4 (AQP4) channels. These LC-generated rhythmic changes are thought to provide the mechanical forces necessary for sustaining the metabolic clearance of waste products within the parenchyma. This review seeks to synthesize several recent studies which indicate that LC-generated vasomotion correlates with both the structure and progression of sleep states, neuronal oscillation patterns, and metabolic states, and that dysfunction of this LC-generated rhythm may contribute to pathological features associated with Alzheimer\u2019s disease, Parkinson\u2019s disease, and small-vessel disease. Understanding the mechanisms of clearance within the brain as a physiologically tunable system will allow researchers to view brain clearance as an adaptive neuro-modulatory function rather than merely as a passive event. Therefore, the focus of this review is on identifying the potential applications of advancements in the field of physiological imaging, molecular biomarkers, and neuro-modulatory or vascular-based therapies for early detection and therapeutic manipulation of clearance processes. Understanding these mechanisms will potentially lead to enhanced cognitive resilience and immune regulation, and promote healthy brain aging.<\/jats:p>","DOI":"10.3390\/ijms262311444","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:56:34Z","timestamp":1764165394000},"page":"11444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Noradrenergic Slow Vasomotion: The Hidden Fluid Pump Linking Sleep, Brain Clearance, and Dementia Pathogenesis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3189-2027","authenticated-orcid":false,"given":"Marius Gabriel","family":"Dabija","sequence":"first","affiliation":[{"name":"Puls Med Association, 051885 Bucharest, Romania"},{"name":"Faculty of Medicine, University of Medicine and Pharmacy \u201cGrigore T. Popa\u201d, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina-Ioana","family":"Tataru","sequence":"additional","affiliation":[{"name":"Puls Med Association, 051885 Bucharest, Romania"},{"name":"Clinical Department of Ophthalmology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Ophthalmology, Clinical Hospital for Ophthalmological Emergencies, 010464 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian Vasile","family":"Dumitru","sequence":"additional","affiliation":[{"name":"Puls Med Association, 051885 Bucharest, Romania"},{"name":"Department of Pathology, Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 030167 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Octavian","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Puls Med Association, 051885 Bucharest, Romania"},{"name":"Department of Anatomy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mugurel Petrinel","family":"Radoi","sequence":"additional","affiliation":[{"name":"Puls Med Association, 051885 Bucharest, Romania"},{"name":"Department of Neurosurgery, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Department of Vascular Neurosurgery, National Institute of Neurology and Neurovascular Diseases, 077160 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandru Vlad","family":"Ciurea","sequence":"additional","affiliation":[{"name":"Puls Med Association, 051885 Bucharest, Romania"},{"name":"Department of Neurosurgery, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Medical Section, Romanian Academy, 010071 Bucharest, Romania"},{"name":"Neurosurgery Department, Sanador Clinical Hospital, 010991 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioan-Andrei","family":"Petrescu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41586-024-07108-6","article-title":"Neuronal Dynamics Direct Cerebrospinal Fluid Perfusion and Brain Clearance","volume":"627","author":"Drieu","year":"2024","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1038\/s41380-024-02778-0","article-title":"Effects of Sleep on the Glymphatic Functioning and Multimodal Human Brain Network Affecting Memory in Older Adults","volume":"30","author":"Ma","year":"2025","journal-title":"Mol. 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