{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T19:27:39Z","timestamp":1793388459212,"version":"4.5.0"},"reference-count":116,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100019493","name":"National Natural Science Foundation of China-Nuclear Technology Innovation Joint Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019493","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>As the most metabolically active organ in the body, there is a recognized need for pathways that remove waste proteins and neurotoxins from the brain. Previous research has indicated potential associations between the clearance system in the brain and the pathological conditions of the central nervous system (CNS), due to its importance, which has attracted considerable attention recently. In the last decade, studies of the clearance system have been restricted to the glymphatic system. However, removal of toxic and catabolic waste by-products cannot be completed independently by the glymphatic system, while no known research or article has focused on a comprehensive overview of the structure and function of the clearance system. This thesis addresses a neglected aspect of linkage between the structural composition and main components as well as the role of neural cells throughout the clearance system, which found evidence that the components of CNS including the glymphatic system and the meningeal lymphatic system interact with a neural cell, such as astrocytes and microglia, to carry out vital clearance functions. As a result of this evidence that can contribute to a better understanding of the clearance system, suggestions were identified for further clinical intervention development of severe conditions caused by the accumulation of metabolic waste products and neurotoxins in the brain, such as Alzheimer\u2019s disease (AD) and Parkinson\u2019s disease (PD).<\/jats:p>","DOI":"10.3389\/fncel.2021.729706","type":"journal-article","created":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T23:56:55Z","timestamp":1643587015000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":41,"title":["Clearance Systems in the Brain, From Structure to Function"],"prefix":"10.3389","volume":"15","author":[{"given":"Jiachen","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzhi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaiqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1007\/s00401-018-1812-4","article-title":"The role of brain barriers in fluid movement in the CNS: is there a \u2018glymphatic\u2019 system?","volume":"135","author":"Abbott","year":"2018","journal-title":"Acta Neuropathol."},{"key":"B2","doi-asserted-by":"crossref","first-page":"C343","DOI":"10.1152\/ajpcell.00095.2018","article-title":"Blood-brain barrier dysfunction in ischemic stroke: targeting tight junctions and transporters for vascular protection.","volume":"315","author":"Abdullahi","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29738","article-title":"Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI.","volume":"6","author":"Absinta","year":"2017","journal-title":"eLife"},{"key":"B4","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1097\/MCP.0000000000000323","article-title":"Sleep deprivation: a mind-body approach.","volume":"22","author":"Aguirre","year":"2016","journal-title":"Curr. Opin. Pulm Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s41586-019-1419-5","article-title":"Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid.","volume":"572","author":"Ahn","year":"2019","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/j.tins.2018.07.007","article-title":"Circadian clocks and sleep: impact of rhythmic metabolism and waste clearance on the brain.","volume":"41","author":"Albrecht","year":"2018","journal-title":"Trends Neurosci."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2019.00001","article-title":"Cerebrovascular smooth muscle cells as the drivers of intramural periarterial drainage of the brain.","volume":"11","author":"Aldea","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.ijdevneu.2018.03.002","article-title":"Neurogenesis in the postnatal cerebellum after injury.","volume":"67","author":"Andreotti","year":"2018","journal-title":"Int. J. Dev. Neurosci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"651","DOI":"10.3892\/ijo.2020.4966","article-title":"New drugs are not enough-drug repositioning in oncology: an update.","volume":"56","author":"Armando","year":"2020","journal-title":"Int. J. Oncol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1038\/nn.4132","article-title":"Depletion of microglia and inhibition of exosome synthesis halt tau propagation.","volume":"18","author":"Asai","year":"2015","journal-title":"Nat. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1084\/jem.20142290","article-title":"A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules.","volume":"212","author":"Aspelund","year":"2015","journal-title":"J. Exp. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1038\/s41593-018-0192-3","article-title":"Epigenetic regulation of brain region-specific microglia clearance activity.","volume":"21","author":"Ayata","year":"2018","journal-title":"Nat. Neurosci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s10571-015-0273-8","article-title":"Lymphatic clearance of the brain: perivascular, paravascular and significance for neurodegenerative diseases.","volume":"36","author":"Bakker","year":"2016","journal-title":"Cell Mol. Neurobiol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-015-0019-5","article-title":"Clearance from the mouse brain by convection of interstitial fluid towards the ventricular system.","volume":"12","author":"Bedussi","year":"2015","journal-title":"Fluids Barriers CNS"},{"key":"B15","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1177\/1073858417691030","article-title":"The glymphatic pathway: waste removal from the CNS via cerebrospinal fluid transport.","volume":"23","author":"Benveniste","year":"2017","journal-title":"Neuroscientist"},{"key":"B16","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1159\/000490349","article-title":"The glymphatic system and waste clearance with brain aging: a review.","volume":"65","author":"Benveniste","year":"2019","journal-title":"Gerontology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"471","DOI":"10.5966\/sctm.2016-0007","article-title":"Novel peripherally derived neural-like stem cells as therapeutic carriers for treating glioblastomas.","volume":"6","author":"Birbrair","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"B18","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.mod.2015.07.007","article-title":"Formation and maintenance of the BBB.","volume":"138","author":"Blanchette","year":"2015","journal-title":"Mech. Dev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.3233\/JAD-180367","article-title":"Targeted assessment of enlargement of the perivascular space in alzheimer\u2019s disease and vascular dementia subtypes implicates astroglial involvement specific to Alzheimer\u2019s disease.","volume":"66","author":"Boespflug","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1093\/cvr\/cvy113","article-title":"Understanding the role of the perivascular space in cerebral small vessel disease.","volume":"114","author":"Brown","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/978-3-030-02601-1_8","article-title":"Ca(2+) signalling in pericytes.","volume":"1109","author":"Burdyga","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00017","article-title":"Biophysical insights into how surfaces, including lipid membranes, modulate protein aggregation related to neurodegeneration.","volume":"4","author":"Burke","year":"2013","journal-title":"Front. Neurol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.celrep.2016.06.033","article-title":"Developmental apoptosis mediates entry and positioning of microglia in the zebrafish brain.","volume":"16","author":"Casano","year":"2016","journal-title":"Cell Rep."},{"key":"B24","first-page":"238","article-title":"How does the brain remove its waste metabolites from within?","volume":"11","author":"Cheng","year":"2019","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.freeradbiomed.2019.07.029","article-title":"Alcohol promotes waste clearance in the CNS via brain vascular reactivity.","volume":"143","author":"Cheng","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.neuron.2018.09.022","article-title":"The meningeal lymphatic system: a new player in neurophysiology.","volume":"100","author":"Da Mesquita","year":"","journal-title":"Neuron"},{"key":"B27","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/s41586-018-0368-8","article-title":"Functional aspects of meningeal lymphatics in ageing and Alzheimer\u2019s disease.","volume":"560","author":"Da Mesquita","year":"","journal-title":"Nature"},{"key":"B28","doi-asserted-by":"publisher","first-page":"583","DOI":"10.15252\/embj.201694591","article-title":"Young microglia restore amyloid plaque clearance of aged microglia.","volume":"36","author":"Daria","year":"2017","journal-title":"EMBO J."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1002\/glia.22960","article-title":"Into rather unexplored terrain-transcellular transport across the blood-brain barrier.","volume":"64","author":"De Bock","year":"2016","journal-title":"Glia"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0229702","article-title":"Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor.","volume":"15","author":"Debacker","year":"2020","journal-title":"PLoS One"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01269","article-title":"A novel model of mixed vascular dementia incorporating hypertension in a rat model of Alzheimer\u2019s disease.","volume":"10","author":"Denver","year":"2019","journal-title":"Front. Physiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3009","DOI":"10.1080\/13880209.2016.1199044","article-title":"Borneol increases blood-tumour barrier permeability by regulating the expression levels of tight junction-associated proteins.","volume":"54","author":"Duan","year":"2016","journal-title":"Pharm. Biol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1007\/s00401-015-1524-y","article-title":"Microglia-blood vessel interactions: a double-edged sword in brain pathologies.","volume":"131","author":"Dudvarski Stankovic","year":"2016","journal-title":"Acta Neuropathol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"710","DOI":"10.7150\/thno.19154","article-title":"General anesthesia inhibits the activity of the \u201cGlymphatic System\u201d.","volume":"8","author":"Gakuba","year":"2018","journal-title":"Theranostics"},{"key":"B35","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1042\/CS20171634","article-title":"The pericyte-glia interface at the blood-brain barrier.","volume":"132","author":"Giannoni","year":"2018","journal-title":"Clin. Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"5313","DOI":"10.2174\/1381612822666160720163656","article-title":"Strategies that target tight junctions for enhanced drug delivery.","volume":"22","author":"Gonzalez-Mariscal","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.2819","article-title":"Magnetic resonance imaging and histopathological visualization of human dural lymphatic vessels.","volume":"8","author":"Ha","year":"2018","journal-title":"Bio Protoc."},{"key":"B38","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1146\/annurev-cellbio-100616-060509","article-title":"Microglia and the brain: complementary partners in development and disease.","volume":"34","author":"Hammond","year":"2018","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2576","DOI":"10.1093\/brain\/awaa179","article-title":"Impaired glymphatic function and clearance of tau in an Alzheimer\u2019s disease model.","volume":"143","author":"Harrison","year":"2020","journal-title":"Brain"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34028","article-title":"Non-invasive imaging of CSF-mediated brain clearance pathways via assessment of perivascular fluid movement with diffusion tensor MRI.","volume":"7","author":"Harrison","year":"2018","journal-title":"eLife"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.1523\/JNEUROSCI.2223-19.2020","article-title":"Meningeal lymphangiogenesis and enhanced glymphatic activity in mice with chronically implanted EEG electrodes.","volume":"40","author":"Hauglund","year":"2020","journal-title":"J. Neurosci."},{"key":"B42","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/s41593-018-0242-x","article-title":"Microglia in neurodegeneration.","volume":"21","author":"Hickman","year":"2018","journal-title":"Nat. Neurosci."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003748","article-title":"A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta.","volume":"4","author":"Iliff","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2583","DOI":"10.1007\/s11064-015-1581-6","article-title":"The glymphatic system: a Beginner\u2019s guide.","volume":"40","author":"Jessen","year":"2015","journal-title":"Neurochem. Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.2174\/1570159X15666170613083606","article-title":"Recent advances in pathophysiology of traumatic brain injury.","volume":"16","author":"Kaur","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1500472","article-title":"Autoregulated paracellular clearance of amyloid-beta across the blood-brain barrier.","volume":"1","author":"Keaney","year":"2015","journal-title":"Sci. Adv."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1111\/epi.16019","article-title":"A pericyte-glia scarring develops at the leaky capillaries in the hippocampus during seizure activity.","volume":"60","author":"Klement","year":"2019","journal-title":"Epilepsia"},{"key":"B48","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1002\/ana.24271","article-title":"Impairment of paravascular clearance pathways in the aging brain.","volume":"76","author":"Kress","year":"2014","journal-title":"Ann. Neurol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1093\/qjmed\/hcy241","article-title":"A brief review of recent discoveries in human anatomy.","volume":"112","author":"Kumar","year":"2019","journal-title":"QJM"},{"key":"B50","first-page":"287","article-title":"[Probable modification of the lymphatic fissures of the walls of the venous sinuses of the dura mater].","volume":"64","author":"Lecco","year":"1953","journal-title":"Arch. Ital. Otol. Rinol. Laringol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/nri.2017.125","article-title":"Microglia and macrophages in brain homeostasis and disease.","volume":"18","author":"Li","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.brainres.2010.02.054","article-title":"Metalloproteinase mediated occludin cleavage in the cerebral microcapillary endothelium under pathological conditions.","volume":"1326","author":"Lischper","year":"2010","journal-title":"Brain Res."},{"key":"B53","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.expneurol.2015.08.018","article-title":"Microglia in the TBI brain: the good, the bad, and the dysregulated.","volume":"275","author":"Loane","year":"2016","journal-title":"Exp. Neurol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"3210","DOI":"10.1172\/JCI90603","article-title":"Understanding the functions and relationships of the glymphatic system and meningeal lymphatics.","volume":"127","author":"Louveau","year":"2017","journal-title":"J. Clin. Invest."},{"key":"B55","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature14432","article-title":"Structural and functional features of central nervous system lymphatic vessels.","volume":"523","author":"Louveau","year":"2015","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"publisher","first-page":"2112","DOI":"10.1177\/0271678X16661202","article-title":"Glymphatic clearance controls state-dependent changes in brain lactate concentration.","volume":"37","author":"Lundgaard","year":"2017","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.689098","article-title":"The glymphatic system: a novel therapeutic target for stroke treatment.","volume":"13","author":"Lv","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01484-6","article-title":"Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice.","volume":"8","author":"Ma","year":"2017","journal-title":"Nat. Commun."},{"key":"B59","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.nbd.2016.08.011","article-title":"The choroid plexus in health and in disease: dialogues into and out of the brain.","volume":"107","author":"Marques","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"B60","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1074\/jbc.R116.760215","article-title":"The translational significance of the neurovascular unit.","volume":"292","author":"McConnell","year":"2017","journal-title":"J. Biol. Chem."},{"key":"B61","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1089\/rej.2013.1530","article-title":"Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases.","volume":"16","author":"Mendelsohn","year":"2013","journal-title":"Rejuvenation Res."},{"key":"B62","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1042\/CS20160381","article-title":"Perivascular spaces, glymphatic dysfunction, and small vessel disease.","volume":"131","author":"Mestre","year":"2017","journal-title":"Clin. Sci."},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07318-3","article-title":"Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension.","volume":"9","author":"Mestre","year":"2018","journal-title":"Nat. Commun."},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030571","article-title":"Dual roles of astrocyte-derived factors in regulation of blood-brain barrier function after brain damage.","volume":"20","author":"Michinaga","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1111\/apha.12250","article-title":"The neurovascular unit - concept review.","volume":"210","author":"Muoio","year":"2014","journal-title":"Acta Physiol. (Oxf)"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.639140","article-title":"Glymphatic system as a gateway to connect neurodegeneration from periphery to CNS.","volume":"15","author":"Natale","year":"2021","journal-title":"Front. Neurosci."},{"key":"B67","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1038\/s41588-020-0696-0","article-title":"An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer\u2019s disease.","volume":"52","author":"Nativio","year":"2020","journal-title":"Nat. Genet."},{"key":"B68","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1126\/science.abb8739","article-title":"Glymphatic failure as a final common pathway to dementia.","volume":"370","author":"Nedergaard","year":"2020","journal-title":"Science"},{"key":"B69","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1002\/epi4.12302","article-title":"Central nervous system lymphatic unit, immunity, and epilepsy: is there a link?","volume":"4","author":"No\u00e9","year":"2019","journal-title":"Epilepsia Open"},{"key":"B70","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/B978-0-444-63432-0.00003-7","article-title":"The blood-brain barrier.","volume":"133","author":"Obermeier","year":"2016","journal-title":"Handb. Clin. Neurol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/j.neuroimage.2018.12.026","article-title":"Non-invasive MRI of brain clearance pathways using multiple echo time arterial spin labelling: an aquaporin-4 study.","volume":"188","author":"Ohene","year":"2019","journal-title":"Neuroimage"},{"key":"B72","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1016\/j.stemcr.2020.03.011","article-title":"Altered brain endothelial cell phenotype from a familial alzheimer mutation and its potential implications for amyloid clearance and drug delivery.","volume":"14","author":"Oikari","year":"2020","journal-title":"Stem Cell Reports"},{"key":"B73","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1002\/glia.20967","article-title":"Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer\u2019s disease.","volume":"58","author":"Olabarria","year":"2010","journal-title":"Glia"},{"key":"B74","doi-asserted-by":"publisher","first-page":"2258","DOI":"10.1177\/0271678X18791632","article-title":"Effects of traumatic brain injury on sleep and enlarged perivascular spaces.","volume":"39","author":"Opel","year":"2019","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B75","doi-asserted-by":"publisher","first-page":"2161","DOI":"10.1007\/s11064-020-03076-1","article-title":"Brain microvascular endothelial cell derived exosomes potently ameliorate cognitive dysfunction by enhancing the clearance of abeta through up-regulation of P-gp in mouse model of AD.","volume":"45","author":"Pan","year":"2020","journal-title":"Neurochem. Res."},{"key":"B76","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.nbd.2016.05.015","article-title":"Suppression of glymphatic fluid transport in a mouse model of Alzheimer\u2019s disease.","volume":"93","author":"Peng","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"B77","doi-asserted-by":"publisher","first-page":"2017.e1","DOI":"10.1016\/j.jamda.2020.05.005","article-title":"Biomarkers profile of people with sarcopenia: a cross-sectional analysis from UK biobank.","volume":"21","author":"Petermann-Rocha","year":"2020","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-019-0799-4","article-title":"Linking traumatic brain injury, sleep disruption and post-traumatic headache: a potential role for glymphatic pathway dysfunction.","volume":"23","author":"Piantino","year":"2019","journal-title":"Curr. Pain Headache Rep."},{"key":"B79","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1146\/annurev-pathol-051217-111018","article-title":"The glymphatic system in central nervous system health and disease: past. present, and future.","volume":"13","author":"Plog","year":"2018","journal-title":"Annu. Rev. Pathol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"104","DOI":"10.5607\/en.2019.28.1.104","article-title":"Persistent malfunction of glymphatic and meningeal lymphatic drainage in a mouse model of subarachnoid hemorrhage.","volume":"28","author":"Pu","year":"2019","journal-title":"Exp. Neurobiol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/S1474-4422(18)30318-1","article-title":"The glymphatic pathway in neurological disorders.","volume":"17","author":"Rasmussen","year":"2018","journal-title":"Lancet Neurol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.molmed.2019.11.008","article-title":"Glymphatic system impairment in Alzheimer\u2019s disease and idiopathic normal pressure hydrocephalus.","volume":"26","author":"Reeves","year":"2020","journal-title":"Trends Mol. Med."},{"key":"B83","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1093\/brain\/awx191","article-title":"Glymphatic MRI in idiopathic normal pressure hydrocephalus.","volume":"140","author":"Ringstad","year":"2017","journal-title":"Brain"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3390\/cells9040851","article-title":"Targeting and crossing the blood-brain barrier with extracellular vesicles.","volume":"9","author":"Saint-Pol","year":"2020","journal-title":"Cells"},{"key":"B85","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1007\/s12264-018-0296-5","article-title":"Pericyte plasticity in the brain.","volume":"35","author":"Santos","year":"2019","journal-title":"Neurosci. Bull."},{"key":"B86","doi-asserted-by":"publisher","first-page":"8296","DOI":"10.1007\/s12035-019-01672-z","article-title":"Influence of matrix metallopeptidase 9 on beta-amyloid elimination across the blood-brain barrier.","volume":"56","author":"Shackleton","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173009","article-title":"Therapeutic drugs modulate ATP-Binding cassette transporter-mediated transport of amyloid beta(1-42) in brain microvascular endothelial cells.","volume":"874","author":"Shubbar","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2020.116581","article-title":"Cardiac and respiration-induced brain deformations in humans quantified with high-field MRI.","volume":"210","author":"Sloots","year":"2020","journal-title":"Neuroimage"},{"key":"B89","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.pneurobio.2017.08.007","article-title":"Lymphatic drainage system of the brain: a novel target for intervention of neurological diseases.","volume":"16","author":"Sun","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/nn.4288","article-title":"Pericytes of the neurovascular unit: key functions and signaling pathways.","volume":"19","author":"Sweeney","year":"2016","journal-title":"Nat. Neurosci."},{"key":"B91","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1152\/physrev.00050.2017","article-title":"Blood-Brain barrier: from physiology to disease and back.","volume":"99","author":"Sweeney","year":"2019","journal-title":"Physiol. Rev."},{"key":"B92","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.mric.2021.01.002","article-title":"Neurofluid as assessed by diffusion-weighted imaging.","volume":"29","author":"Taoka","year":"2021","journal-title":"Magn. Reson. Imaging Clin. N. Am."},{"key":"B93","doi-asserted-by":"publisher","first-page":"111","DOI":"10.2463\/mrms.rev.2017-0116","article-title":"Gadolinium-based contrast media, cerebrospinal fluid and the glymphatic system: possible mechanisms for the deposition of gadolinium in the brain.","volume":"17","author":"Taoka","year":"2018","journal-title":"Magn. Reson. Med. Sci."},{"key":"B94","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1002\/jmri.26892","article-title":"Glymphatic imaging using MRI.","volume":"51","author":"Taoka","year":"2020","journal-title":"J. Magn. Reson. Imaging"},{"key":"B95","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1097\/RLI.0000000000000473","article-title":"Impact of the glymphatic system on the kinetic and distribution of gadodiamide in the rat brain: observations by dynamic MRI and effect of circadian rhythm on tissue gadolinium concentrations.","volume":"53","author":"Taoka","year":"2018","journal-title":"Invest. Radiol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1007\/s11604-017-0617-z","article-title":"Evaluation of glymphatic system activity with the diffusion MR technique: diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer\u2019s disease cases.","volume":"35","author":"Taoka","year":"2017","journal-title":"Jpn. J. Radiol."},{"key":"B97","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1083\/jcb.201412147","article-title":"Brain barriers: crosstalk between complex tight junctions and adherens junctions.","volume":"209","author":"Tietz","year":"2015","journal-title":"J. Cell Biol."},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20102600","article-title":"Disturbance of intracerebral fluid clearance and blood-brain barrier in vascular cognitive impairment.","volume":"20","author":"Ueno","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01656","article-title":"Altered waste disposal system in aging and Alzheimer\u2019s disease: focus on astrocytic Aquaporin-4.","volume":"10","author":"Valenza","year":"2019","journal-title":"Front. Pharmacol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.semcdb.2014.08.011","article-title":"Architecture of tight junctions and principles of molecular composition.","volume":"36","author":"Van Itallie","year":"2014","journal-title":"Semin. Cell Dev. Biol."},{"key":"B101","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.neubiorev.2018.03.028","article-title":"Interaction between blood-brain barrier and glymphatic system in solute clearance.","volume":"90","author":"Verheggen","year":"2018","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B102","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1080\/14728222.2017.1398236","article-title":"The aquaporin-4 water channel as a potential drug target in neurological disorders.","volume":"21","author":"Verkman","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"B103","doi-asserted-by":"publisher","first-page":"3683","DOI":"10.1177\/0271678X17697340","article-title":"Region-specific permeability of the blood-brain barrier upon pericyte loss.","volume":"37","author":"Villasenor","year":"2017","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"B104","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.neulet.2017.11.001","article-title":"Lymphatic vasculature in human dural superior sagittal sinus: implications for neurodegenerative proteinopathies.","volume":"665","author":"Visanji","year":"2018","journal-title":"Neurosci. Lett."},{"key":"B105","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1111\/bpa.12656","article-title":"Deep cervical lymph node ligation aggravates AD-like pathology of APP\/PS1 mice.","volume":"29","author":"Wang","year":"2019","journal-title":"Brain Pathol."},{"key":"B106","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41582-020-0312-z","article-title":"Perivascular spaces in the brain: anatomy, physiology and pathology.","volume":"16","author":"Wardlaw","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2019.1681444","article-title":"Long-term consumption of alcohol exacerbates neural lesions by destroying the functional integrity of the blood-brain barrier.","author":"Wei","year":"2019","journal-title":"Drug Chem. Toxicol."},{"key":"B108","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.neubiorev.2018.09.027","article-title":"Disturbances of sleep quality, timing and structure and their relationship with other neuropsychiatric symptoms in Alzheimer\u2019s disease and schizophrenia: insights from studies in patient populations and animal models.","volume":"97","author":"Winsky-Sommerer","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B109","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1039\/c7mt00288b","article-title":"Zinc ions regulate opening of tight junction favouring efflux of macromolecules via the GSK3beta\/snail-mediated pathway.","volume":"10","author":"Xiao","year":"2018","journal-title":"Metallomics"},{"key":"B110","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3233\/JAD-160957","article-title":"AQP4 association with amyloid deposition and astrocyte pathology in the Tg-arcswe mouse model of Alzheimer\u2019s disease.","volume":"57","author":"Yang","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/5675014","article-title":"Diagnostic performance of glymphatic system evaluation using diffusion tensor imaging in idiopathic normal pressure hydrocephalus and mimickers.","volume":"2019","author":"Yokota","year":"2019","journal-title":"Curr. Gerontol. Geriatr. Res."},{"key":"B112","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1001\/jamaneurol.2016.4370","article-title":"Association of perivascular localization of Aquaporin-4 with cognition and Alzheimer disease in aging brains.","volume":"74","author":"Zeppenfeld","year":"2017","journal-title":"JAMA Neurol."},{"key":"B113","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1136\/svn-2018-000203","article-title":"Role of the glymphatic system in ageing and diabetes mellitus impaired cognitive function.","volume":"4","author":"Zhang","year":"2019","journal-title":"Stroke Vasc. Neurol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1111\/cns.13194","article-title":"Aquaporin 4 deletion exacerbates brain impairments in a mouse model of chronic sleep disruption.","volume":"26","author":"Zhang","year":"2020","journal-title":"CNS Neurosci. Ther."},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20795-9","article-title":"A circadian clock regulates efflux by the blood-brain barrier in mice and human cells.","volume":"12","author":"Zhang","year":"2021","journal-title":"Nat. Commun."},{"key":"B116","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1002\/ana.25670","article-title":"Impairment of the glymphatic pathway and putative meningeal lymphatic vessels in the aging human.","volume":"87","author":"Zhou","year":"2020","journal-title":"Ann. Neurol."}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2021.729706\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,30]],"date-time":"2022-01-30T23:57:01Z","timestamp":1643587021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2021.729706\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,31]]},"references-count":116,"alternative-id":["10.3389\/fncel.2021.729706"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2021.729706","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,31]]},"article-number":"729706"}}