Cited by 2,075Cerebrospinal fluid and hydrocephalusTraumatic Brain Injury and Neurovascular DisturbancesBarrier Structure and Function Studies

The DOI matches its Crossref record; 141 of the 141 references it cites were found in a registry or an index.

The glymphatic system: a beginner's guide

Open access

Jessen, Nadia Aalling, Munk, Anne Sofie Finmann, Lundgaard, Iben, Nedergaard, Maiken·2015·Neurochemical Research

DOI 10.1007/s11064-015-1581-6PMC PMC4636982

Open this paper in CoChat — free account

Abstract

The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular tunnels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system. Besides waste elimination, the glymphatic system also facilitates brain-wide distribution of several compounds, including glucose, lipids, amino acids, growth factors, and neuromodulators. Intriguingly, the glymphatic system function mainly during sleep and is largely disengaged during wakefulness. The biological need for sleep across all species may therefore reflect that the brain must enter a state of activity that enables elimination of potentially neurotoxic waste products, including β-amyloid. Since the concept of the glymphatic system is relatively new, we will here review its basic structural elements, organization, regulation, and functions. We will also discuss recent studies indicating that glymphatic function is suppressed in various diseases and that failure of glymphatic function in turn might contribute to pathology in neurodegenerative disorders, traumatic brain injury and stroke.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1007/s11064-015-1581-6

Cites

141 of 141 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β
Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., Benveniste, H., Vates, G. E., Deane, R., Goldman, S. A., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003748 · Cited by 5,824
Self-citation
Sleep Drives Metabolite Clearance from the Adult Brain
Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., O’Donnell, J., Christensen, D. J., Nicholson, C., Iliff, J. J., et al. (2013) · Science · doi:10.1126/science.1241224 · Cited by 5,411
Self-citation
Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.
Strittmatter, W. J., Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.1977 · Cited by 4,268 · cited 1×
“maintaining homeostasis necessary for a healthy environment of the brain [60, 61].”
Protein aggregation and neurodegenerative disease
Ross, C. A., & Poirier, M. A. (2004) · Nature Medicine · doi:10.1038/nm1066 · Cited by 3,454
Primary Progressive Aphasia
Weıntraub, S. (1990) · Archives of Neurology · doi:10.1001/archneur.1990.00530120075013 · Cited by 3,018
Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969
The locus coeruleus–noradrenergic system: modulation of behavioral state and state-dependent cognitive processes
Berridge, C. W., & Waterhouse, B. D. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(03)00143-7 · Cited by 2,529
Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia
Joutel, A., Corpechot, C., Ducros, A., Vahedi, K., Chabriat, H., Mouton, P., Alamowitch, S., Domenga, V., Cécillion, M., Maréchal, E., et al. (1996) · Nature · doi:10.1038/383707a0 · Cited by 2,068
Local sleep and learning
Huber, R., Felice Ghilardi, M., Massimini, M., & Tononi, G. (2004) · Nature · doi:10.1038/nature02663 · Cited by 1,854

Show all 141 references

Sorted by citations

Items 101–200 of 1,000

Iron, Neuroinflammation and Neurodegeneration
Ward, R. J., Dexter, D. T., & Crichton, R. R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137267 · Cited by 144
Nonsurgical therapy for hydrocephalus: a comprehensive and critical review
Bigio, M. R. D., & Curzio, D. L. D. (2015) · Fluids and Barriers of the CNS · doi:10.1186/s12987-016-0025-2 · Cited by 144
Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue
Jošt, G., Frenzel, T., Lohrke, J., Lenhard, D. C., Naganawa, S., & Pietsch, H. (2016) · European Radiology · doi:10.1007/s00330-016-4654-2 · Cited by 144
From Stroke to Dementia: a Comprehensive Review Exposing Tight Interactions Between Stroke and Amyloid-β Formation
Goulay, R., Romo, L. M., Hol, E. M., & Dijkhuizen, R. M. (2019) · Translational Stroke Research · doi:10.1007/s12975-019-00755-2 · Cited by 144
Voluntary running enhances glymphatic influx in awake behaving, young mice
von Holstein-Rathlou, S., Petersen, N. C., & Nedergaard, M. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2017.10.035 · Cited by 147
Self-citation
The Neurovascular Unit Dysfunction in Alzheimer’s Disease
Soto-Rojas, L. O., Pacheco‐Herrero, M., Martínez-Gómez, P. A., Campa-Córdoba, B. B., Apátiga-Pérez, R., Villegas-Rojas, M. M., Harrington, C. R., de la Cruz, F., Garcés‐Ramírez, L., & Luna‐Muñoz, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042022 · Cited by 146
Neurovascular Interactions in the Nervous System
Segarra, M., Aburto, M. R., Hefendehl, J. K., & Acker‐Palmer, A. (2019) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100818-125142 · Cited by 137
Biology and Models of the Blood–Brain Barrier
Hajal, C., Roi, B. L., Kamm, R. D., & Maoz, B. M. (2021) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-082120-042814 · Cited by 143
A Brief Overview of the Cerebrospinal Fluid System and Its Implications for Brain and Spinal Cord Diseases
Wichmann, T. O., Damkier, H. H., & Pedersen, M. (2022) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2021.737217 · Cited by 141
Sleep and β-Amyloid Deposition in Alzheimer Disease: Insights on Mechanisms and Possible Innovative Treatments
Cordone, S., Annarumma, L., Rossini, P. M., & Gennaro, L. D. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00695 · Cited by 143
The homeostatic astroglia emerges from evolutionary specialization of neural cells
Verkhratsky, A., & Nedergaard, M. (2016) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2015.0428 · Cited by 133
Self-citation
Respiratory influence on cerebrospinal fluid flow – a computational study based on long-term intracranial pressure measurements
Vinje, V., Ringstad, G. A., Lindstrøm, E. K., Valnes, L. M., Rognes, M. E., Eide, P. K., & Mardal, K. (2019) · Scientific Reports · doi:10.1038/s41598-019-46055-5 · Cited by 132
Glymphatic system disruption as a mediator of brain trauma and chronic traumatic encephalopathy
Sullan, M. J., Asken, B. M., Jaffee, M. S., DeKosky, S. T., & Bauer, R. M. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.08.016 · Cited by 135
Blood biomarkers in ischemic stroke: potential role and challenges in clinical practice and research
Makris, K., Haliassos, A., Chondrogianni, M. E., & Tsivgoulis, G. K. (2018) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408363.2018.1461190 · Cited by 130
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease
Duperron, M., Knol, M. J., Grand, Q. L., Evans, T. E., Mishra, A., Tsuchida, A., Roshchupkin, G. V., Konuma, T., Trégouët, D., Romero, J. R., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02268-w · Cited by 138
New insights into coupling and uncoupling of cerebral blood flow and metabolism in the brain
Venkat, P., Chopp, M., & Chen, J. (2016) · Croatian Medical Journal · doi:10.3325/cmj.2016.57.223 · Cited by 138
Gd-based Contrast Enhancement of the Perivascular Spaces in the Basal Ganglia
Naganawa, S., Nakane, T., Kawai, H., & Taoka, T. (2016) · Magnetic Resonance in Medical Sciences · doi:10.2463/mrms.mp.2016-0039 · Cited by 129
Role of choroid plexus in cerebrospinal fluid hydrodynamics
Orešković, D., Radoš, M., & Klarica, M. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.04.025 · Cited by 133
Sex differences in age-related changes in the sleep-wake cycle
Carrier, J., Semba, K., Deurveilher, S., Drogos, L. L., Cyr-Cronier, J., Lord, C., & Sekerovick, Z. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.07.004 · Cited by 139
Gadolinium-Based Contrast Agent-Related Toxicities
Pasquini, L., Napolitano, A., Visconti, E., Longo, D., Romano, A., Tomà, P., & Rossi‐Espagnet, M. C. (2018) · CNS Drugs · doi:10.1007/s40263-018-0500-1 · Cited by 129
Evaluation of Glymphatic System Using Diffusion MR Technique in T2DM Cases
Yang, G., Deng, N., Liu, Y., Gu, Y., & Yao, X. (2020) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2020.00300 · Cited by 130
Blood biomarkers for mild traumatic brain injury: a selective review of unresolved issues
Hier, D. B., Obafemi-Ajayi, T., Thimgan, M. S., Olbricht, G. R., Azizi, S., Allen, B., Hadi, B., & Wunsch, D. C. (2021) · Biomarker Research · doi:10.1186/s40364-021-00325-5 · Cited by 130
Molecular and metabolic heterogeneity of astrocytes and microglia
Hasel, P., Aisenberg, W. H., Bennett, F. C., & Liddelow, S. A. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.03.006 · Cited by 135
White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies
Venkat, P., Chopp, M., Zacharek, A., Cui, C., Zhang, L., Li, Q., Lü, M., Zhang, T., Liu, A., & Chen, J. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.11.002 · Cited by 128
Modeling Alzheimer's disease with human induced pluripotent stem (iPS) cells
Mungenast, A. E., Siegert, S., & Tsai, L. (2015) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2015.11.010 · Cited by 136
Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions
Acaz‐Fonseca, E., Ávila-Rodriguez, M., García‐Segura, L. M., & Barreto, G. E. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.06.002 · Cited by 131
Immunotherapies for malignant glioma
Boussiotis, V. A., & Charest, A. (2017) · Oncogene · doi:10.1038/s41388-017-0024-z · Cited by 126
Current Concepts in Intracranial Interstitial Fluid Transport and the Glymphatic System: Part I—Anatomy and Physiology
Klostranec, J. M., Vucevic, D., Bhatia, K. D., Kortman, H. G. J., Krings, T., Murphy, K., terBrugge, K. G., & Mikulis, D. J. (2021) · Radiology · doi:10.1148/radiol.2021202043 · Cited by 130
Cerebral small vessel disease alters neurovascular unit regulation of microcirculation integrity involved in vascular cognitive impairment
Yang, Q. Z., Wei, X., Deng, B., Chang, Z., Jin, D., Huang, Y., Zhang, J. H., Yenari, M. A., Jin, K., & Wang, Q. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105750 · Cited by 138
Cannula Implantation into the Cisterna Magna of Rodents
Xavier, A. L. R., Hauglund, N. L., von Holstein‐Rathlou, S., Li, Q., Sanggaard, S., Lou, N., Lundgaard, I., & Nedergaard, M. (2018) · Journal of Visualized Experiments · doi:10.3791/57378 · Cited by 127
Self-citation
Global and Regional Changes in Perivascular Space in Idiopathic and Familial Parkinson's Disease
Donahue, E. K., Murdos, A., Jakowec, M. W., Sheikh‐Bahaei, N., Toga, A. W., Petzinger, G. M., & Sepehrband, F. (2021) · Movement Disorders · doi:10.1002/mds.28473 · Cited by 124
Astrocyte-Neuron Metabolic Crosstalk in Neurodegeneration: A Mitochondrial Perspective
Mulica, P., Grünewald, A., & Pereira, S. L. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.668517 · Cited by 126
Where are we? The anatomy of the murine cortical meninges revisited for intravital imaging, immunology, and clearance of waste from the brain
Coles, J. A., Myburgh, E., Brewer, J. M., & McMenamin, P. G. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.05.002 · Cited by 123
Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function
Lundgaard, I., Wang, W., Eberhardt, A., Vinitsky, H. S., Reeves, B. C., Peng, S., Lou, N., Hussain, R., & Nedergaard, M. (2018) · Scientific Reports · doi:10.1038/s41598-018-20424-y · Cited by 136
Self-citation
Revisiting the blood-brain barrier: A hard nut to crack in the transportation of drug molecules
Harilal, S., Jose, J., Parambi, D. G. T., Kumar, R., Unnikrishnan, M. K., Uddin, M. S., Mathew, G. E., Pratap, R., Marathakam, A., & Mathew, B. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.03.018 · Cited by 127
Current Concepts in Intracranial Interstitial Fluid Transport and the Glymphatic System: Part II—Imaging Techniques and Clinical Applications
Klostranec, J. M., Vucevic, D., Bhatia, K. D., Kortman, H. G. J., Krings, T., Murphy, K., terBrugge, K. G., & Mikulis, D. J. (2021) · Radiology · doi:10.1148/radiol.2021204088 · Cited by 121
Astrocytes and the modulation of sleep
Haydon, P. G. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.02.008 · Cited by 128
Altered Brain Glymphatic Flow at Diffusion-Tensor MRI in Rapid Eye Movement Sleep Behavior Disorder
Bae, Y. J., Kim, J., Choi, B. S., Ryoo, N., Song, Y. S., Nam, Y., Yoon, I., Cho, S. J., & Kim, J. H. (2023) · Radiology · doi:10.1148/radiol.221848 · Cited by 121
The Glymphatic System: A Review of the Challenges in Visualizing its Structure and Function with MR Imaging
Naganawa, S., & Taoka, T. (2020) · Magnetic Resonance in Medical Sciences · doi:10.2463/mrms.rev.2020-0122 · Cited by 122
Derivation and transcriptional reprogramming of border-forming wound repair astrocytes after spinal cord injury or stroke in mice
O’Shea, T. M., Ao, Y., Wang, S., Ren, Y., Cheng, A. L., Kawaguchi, R., Shi, Z., Swarup, V., & Sofroniew, M. V. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01684-6 · Cited by 129
The Many Faces of Astrocytes in Alzheimer's Disease
Monterey, M. D., Wei, H., Wu, X., & Wu, J. Q. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.619626 · Cited by 117
Perivascular Spaces, Glymphatic System and MR
Yu, L., Hu, X., Li, H., & Zhao, Y. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.844938 · Cited by 118
Obstructive sleep apnoea and Alzheimer’s disease: In search of shared pathomechanisms
Polšek, D., Gildeh, N., Cash, D., Winsky‐Sommerer, R., Williams, S., Turkheimer, F., Leschziner, G. D., Morrell, M. J., & Rosenzweig, I. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.12.004 · Cited by 114
Decreased AQP4 Expression Aggravates ɑ-Synuclein Pathology in Parkinson’s Disease Mice, Possibly via Impaired Glymphatic Clearance
Cui, H., Wang, W., Zheng, X., Xia, D., Liu, H., Qin, C., Tian, H., & Teng, J. (2021) · Journal of Molecular Neuroscience · doi:10.1007/s12031-021-01836-4 · Cited by 115
Astrocytes as a Therapeutic Target in Alzheimer’s Disease–Comprehensive Review and Recent Developments
Rodríguez-Giraldo, M., González-Reyes, R. E., Ramírez-Guerrero, S., Bonilla-Trilleras, C. E., Guardo-Maya, S., & Nava-Mesa, M. O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113630 · Cited by 122
Neuroplasticity and Clinical Practice: Building Brain Power for Health
Shaffer, J. (2016) · Frontiers in Psychology · doi:10.3389/fpsyg.2016.01118 · Cited by 133
Circadian Rhythm and Alzheimer’s Disease
Homolak, J., Mudrovčić, M., Vukić, B., & Toljan, K. (2018) · Medical Sciences · doi:10.3390/medsci6030052 · Cited by 120
Unravelling the regulation of insulin transport across the brain endothelial cell
Gray, S. M., Aylor, K. W., & Barrett, E. J. (2017) · Diabetologia · doi:10.1007/s00125-017-4285-4 · Cited by 109
Glymphatic System as a Gateway to Connect Neurodegeneration From Periphery to CNS
Natale, G., Limanaqi, F., Busceti, C. L., Mastroiacovo, F., Nicoletti, F., Puglisi‐Allegra, S., & Fornai, F. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.639140 · Cited by 116
Quantitative Gd‐DOTA uptake from cerebrospinal fluid into rat brain using 3D VFA‐SPGR at 9.4T
Lee, H., Mortensen, K., Sanggaard, S., Koch, P., Brunner, H., Quistorff, B., Nedergaard, M., & Benveniste, H. (2018) · Magnetic Resonance in Medicine · doi:10.1002/mrm.26779 · Cited by 110
Self-citation
Decoupling of Global Brain Activity and Cerebrospinal Fluid Flow in Parkinson's Disease Cognitive Decline
Han, F., Brown, G. L., Zhu, Y., Belkin-Rosen, A., Lewis, M. M., Du, G., Gu, Y., Eslinger, P. J., Mailman, R. B., Huang, X., et al. (2021) · Movement Disorders · doi:10.1002/mds.28643 · Cited by 111
Hello from the other side: how autoantibodies circumvent the blood-brain barrier in autoimmune encephalitis
Platt, M. P., Agalliu, D., & Cutforth, T. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00442 · Cited by 108
Potential Modes of Intercellular α-Synuclein Transmission
Valdinocci, D., Radford, R. A. W., Siow, S. M., Chung, R. S., & Pountney, D. L. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020469 · Cited by 114
Antisense drugs make sense for neurological diseases
Bennett, C. F., Kordasiewicz, H. B., & Cleveland, D. W. (2021) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010919-023738 · Cited by 108
The relationship between inflammation, impaired glymphatic system, and neurodegenerative disorders: A vicious cycle
Cai, Y., Zhang, Y., Leng, S., Ma, Y., Jiang, Q., Wen, Q., Ju, S., & Hu, J. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106426 · Cited by 120
Effects of Meditation and Music-Listening on Blood Biomarkers of Cellular Aging and Alzheimer’s Disease in Adults with Subjective Cognitive Decline: An Exploratory Randomized Clinical Trial
Innes, K. E., Selfe, T. K., Brundage, K. M., Montgomery, C., Wen, S., Kandati, S., Bowles, H., Khalsa, D. S., & Huysmans, Z. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180164 · Cited by 118
Biochemical Markers in Alzheimer’s Disease
Rabbito, A., Dulewicz, M., Kulczyńska‐Przybik, A., & Mroczko, B. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21061989 · Cited by 105
Physiology and Clinical Relevance of Enlarged Perivascular Spaces in the Aging Brain
Bown, C. W., Carare, R. O., Schrag, M., & Jefferson, A. L. (2021) · Neurology · doi:10.1212/wnl.0000000000013077 · Cited by 107
Cerebrospinal Fluid Flow
Kelley, D. H., & Thomas, J. H. (2022) · Annual Review of Fluid Mechanics · doi:10.1146/annurev-fluid-120720-011638 · Cited by 113
Cerebrospinal fluid levels of orexin-A and histamine, and sleep profile within the Alzheimer process
Gabelle, A., Jaussent, I., Hirtz, C., Vialaret, J., Navucet, S., Grasselli, C., Robert, P., Lehmann, S., & Dauvilliers, Y. A. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.01.011 · Cited by 103
Spreading depression as a preclinical model of migraine
Harriott, A. M., Takizawa, T., Chung, D. Y., & Chen, S. (2019) · The Journal of Headache and Pain · doi:10.1186/s10194-019-1001-4 · Cited by 104
The established and emerging roles of astrocytes and microglia in amyotrophic lateral sclerosis and frontotemporal dementia
Radford, R. A. W., Morsch, M., Rayner, S. L., Cole, N. J., Pountney, D. L., & Chung, R. S. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00414 · Cited by 105
Is the glymphatic system the missing link between sleep impairments and neurological disorders? Examining the implications and uncertainties
Christensen, J., Yamakawa, G. R., Shultz, S. R., & Mychasiuk, R. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101917 · Cited by 110
A deep sleep stage in Drosophila with a functional role in waste clearance
van Alphen, B., Semenza, E. R., Yap, M., van Swinderen, B., & Allada, R. (2021) · Science Advances · doi:10.1126/sciadv.abc2999 · Cited by 103
Autonomic arousals contribute to brain fluid pulsations during sleep
Picchioni, D., Özbay, P. S., Mandelkow, H., de Zwart, J. A., Wang, Y., van Gelderen, P., & Duyn, J. H. (2022) · NeuroImage · doi:10.1016/j.neuroimage.2022.118888 · Cited by 104
Transcranial optical imaging reveals a pathway for optimizing the delivery of immunotherapeutics to the brain
Plog, B. A., Mestre, H., Olveda, G. E., Sweeney, A. M., Kenney, H. M., Cove, A., Dholakia, K. Y., Tithof, J., Nevins, T. D., Lundgaard, I., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.120922 · Cited by 102
Self-citation
Waste Clearance in the Brain
Kaur, J., Fahmy, L. M., Davoodi‐Bojd, E., Zhang, L., Ding, G., Hu, J., Zhang, Z., Chopp, M., & Jiang, Q. (2021) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2021.665803 · Cited by 108
Is bulk flow plausible in perivascular, paravascular and paravenous channels?
Faghih, M. M., & Sharp, M. K. (2018) · Fluids and Barriers of the CNS · doi:10.1186/s12987-018-0103-8 · Cited by 101
Sampling Rate Effects on Resting State fMRI Metrics
Huotari, N., Raitamaa, L., Helakari, H., Kananen, J., Raatikainen, V., Rasila, A., Tuovinen, T., Kantola, J., Borchardt, V., Kiviniemi, V. J., et al. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00279 · Cited by 103
Prioritized Research for the Prevention, Treatment, and Reversal of Chronic Disease: Recommendations From the Lifestyle Medicine Research Summit
Yoram Vodovotz, B., Barnard, N. D., Hu, F. B., Jakicic, J. M., Lianov, L. S., Loveland, D., Buysse, D. J., Szigethy, E., Finkel, T., Sowa, G., et al. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.585744 · Cited by 116
The glymphatic system and meningeal lymphatics of the brain: new understanding of brain clearance
Yankova, G., Bogomyakova, O. B., & Тулупов, А. А. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0106 · Cited by 110
Hydraulic resistance of periarterial spaces in the brain
Tithof, J., Kelley, D. H., Mestre, H., Nedergaard, M., & Thomas, J. H. (2019) · Fluids and Barriers of the CNS · doi:10.1186/s12987-019-0140-y · Cited by 101
Self-citation
Pathogenetic pathways of cognitive dysfunction and dementia in metabolic syndrome
Borshchev, Y. Y., Uspensky, Y. P., & Galagudza, M. M. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.116932 · Cited by 97
Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment
Fülöp, G., Tarantini, S., Yabluchanskiy, A., Molnár, A., Prodan, C. I., Kiss, T., Csípő, T., Lipécz, Á., Balasubramanian, P., Farkas, E., et al. (2019) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00776.2018 · Cited by 101
The Air We Breathe: Air Pollution as a Prevalent Proinflammatory Stimulus Contributing to Neurodegeneration
Jankowska-Kieltyka, M., Roman, A., & Nalepa, I. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.647643 · Cited by 99
Burden of Dilated Perivascular Spaces, an Emerging Marker of Cerebral Small Vessel Disease, Is Highly Heritable
Duperron, M., Tzourio, C., Sargurupremraj, M., Mazoyer, B. M., Soumaré, A., Schilling, S., Amouyel, P., Chauhan, G., Zhu, Y., & Debette, S. (2018) · Stroke · doi:10.1161/strokeaha.117.019309 · Cited by 96
An overview of sleep and circadian dysfunction in Parkinson's disease
Mantovani, S., Smith, S. S., Gordon, R., & O’Sullivan, J. D. (2018) · Journal of Sleep Research · doi:10.1111/jsr.12673 · Cited by 105
Local Sleep and Alzheimer’s Disease Pathophysiology
Mander, B. A. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.525970 · Cited by 97
Harnessing cerebrospinal fluid circulation for drug delivery to brain tissues
Naseri Kouzehgarani, G., Feldsien, T., Engelhard, H. H., Mirakhur, K. K., Phipps, C., Nimmrich, V., Clausznitzer, D., & Lefebvre, D. R. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.03.002 · Cited by 95
Posthemorrhagic hydrocephalus development after germinal matrix hemorrhage: Established mechanisms and proposed pathways
Klebe, D. W., McBride, D. W., Krafft, P. R., Flores, J. J., Tang, J., & Zhang, J. H. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24394 · Cited by 92
Repetitive Mild Traumatic Brain Injury Alters Glymphatic Clearance Rates in Limbic Structures of Adolescent Female Rats
Christensen, J., Wright, D. K., Yamakawa, G. R., Shultz, S. R., & Mychasiuk, R. (2020) · Scientific Reports · doi:10.1038/s41598-020-63022-7 · Cited by 96
Magnetic Resonance Imaging–Visible Perivascular Spaces in Basal Ganglia Predict Cognitive Decline in Parkinson's Disease
Park, Y. W., Shin, N., Chung, S. J., Kim, J., Lim, S. M., Lee, P. H., Lee, S., & Ahn, K. J. (2019) · Movement Disorders · doi:10.1002/mds.27798 · Cited by 93
The Role of Neurovascular System in Neurodegenerative Diseases
Ahmad, A., Patel, V., Xiao, J., & Khan, M. M. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02023-z · Cited by 97
Impaired Glymphatic System Actions in Obstructive Sleep Apnea Adults
Roy, B., Nunez, A., Aysola, R., Kang, D. W., Vacas, S., & Kumar, R. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.884234 · Cited by 96
Cerebrospinal Fluid–Basic Concepts Review
Czarniak, N., Kamińska, J., Matowicka-Karna, J., & Koper‐Lenkiewicz, O. M. (2023) · Biomedicines · doi:10.3390/biomedicines11051461 · Cited by 110
Astrocyte-Mediated Neuroinflammation in Neurological Conditions
Zhao, Y., Huang, Y., Cao, Y., & Yang, J. H. (2024) · Biomolecules · doi:10.3390/biom14101204 · Cited by 106
Mechanical stress activates NMDA receptors in the absence of agonists
Maneshi, M. M., Maki, B. A., Gnanasambandam, R., Belin, S., Popescu, G., Sachs, F., & Hua, S. Z. (2017) · Scientific Reports · doi:10.1038/srep39610 · Cited by 92
Cerebrospinal fluid and the early brain development of autism
Shen, M. D. (2018) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-018-9256-7 · Cited by 93
Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?
Moulson, A. J., Squair, J. W., Franklin, R. J. M., Tetzlaff, W., & Assinck, P. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.703810 · Cited by 97
Retinal Vasculopathy in Alzheimer’s Disease
Shi, H., Koronyo, Y., Rentsendorj, A., Fuchs, D.-T. S., Sheyn, J., Black, K. L., Mirzaei, N., & Koronyo‐Hamaoui, M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.731614 · Cited by 91
Glymphatic system: a gateway for neuroinflammation
Zou, K., Deng, Q., Zhang, H., & Huang, C. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.391312 · Cited by 98
AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis
Trillo-Contreras, J. L., Toledo‐Aral, J. J., Echevarrı́a, M., & Villadiego, J. (2019) · Cells · doi:10.3390/cells8020197 · Cited by 95
Obstructive Sleep Apnea in Neurodegenerative Disorders: Current Evidence in Support of Benefit from Sleep Apnea Treatment
Lajoie, A. C., Lafontaine, A., Kimoff, R. J., & Kamińska, M. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9020297 · Cited by 90
Cerebral Small Vessel Disease: a Review of the Pathophysiological Mechanisms
Hannawi, Y. (2023) · Translational Stroke Research · doi:10.1007/s12975-023-01195-9 · Cited by 99
SLC20A2 Deficiency in Mice Leads to Elevated Phosphate Levels in Cerbrospinal Fluid and Glymphatic Pathway‐Associated Arteriolar Calcification, and Recapitulates Human Idiopathic Basal Ganglia Calcification
Wallingford, M. C., Chia, J. J., Leaf, E. M., Borgeia, S., Chavkin, N. W., Sawangmake, C., Marro, K. I., Cox, T. C., Speer, M. Y., & Giachelli, C. M. (2016) · Brain Pathology · doi:10.1111/bpa.12362 · Cited by 88
Cerebrospinal fluid hypersecretion in pediatric hydrocephalus
Karimy, J. K., Durán, D., Hu, J. K., Furey, C. G., Gaillard, J. R., Bayri, Y., Rice, H., DiLuna, M. L., Gerzanich, V., Simard, J. M., et al. (2016) · Neurosurgical FOCUS · doi:10.3171/2016.8.focus16278 · Cited by 90
Induced dural lymphangiogenesis facilities soluble amyloid-beta clearance from brain in a transgenic mouse model of Alzheimer's disease
Yao, Z., Wen, Y.-R., Yang, J.-H., & Wang, X. (2018) · Neural Regeneration Research · doi:10.4103/1673-5374.230299 · Cited by 90
Chronic stress impairs the aquaporin-4-mediated glymphatic transport through glucocorticoid signaling
Wei, F., Song, J. G., Zhang, C., Lin, J., Xue, R., Shan, L., Gong, S., Zhang, G., Qin, Z., Xu, G., et al. (2019) · Psychopharmacology · doi:10.1007/s00213-018-5147-6 · Cited by 96
An Overview on the Differential Interplay Among Neurons–Astrocytes–Microglia in CA1 and CA3 Hippocampus in Hypoxia/Ischemia
Lana, D., Ugolini, F., & Giovannini, M. G. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.585833 · Cited by 92
Glymphatic dysfunction in isolated REM sleep behavior disorder
Lee, D. A., Lee, H., & Park, K. M. (2021) · Acta Neurologica Scandinavica · doi:10.1111/ane.13573 · Cited by 88

Authors: Jessen, N. A., Munk, A. S. F., Lundgaard, I., & Nedergaard, M.
Affiliations: University of Rochester Medicine (US)
ORCID: Jessen, Nadia Aalling
Lundgaard, Iben
Nedergaard, Maiken
Venue: Neurochemical Research
Publisher: Springer Science and Business Media LLC
Published: 2015-05-07
Volume: 40
Issue: 12
Pages: 2583-2599
ISSN: 0364-3190 (ISSN-L)
1573-6903
DOI: 10.1007/s11064-015-1581-6
PMC: PMC4636982
OpenAlex: W211905087
Cited by: 2,075
References: 141
Citations by year: 2026: 230 · 2025: 300 · 2024: 266 · 2023: 235 · 2022: 217 · 2021: 223 · 2020: 168 · 2019: 137 · 2018: 127 · 2017: 102 · 2016: 51 · 2015: 17
FWCI: 45.97
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Neurochemical Research (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Lund University Publications (Lund University) (submittedVersion)
Funders: Israel Science Foundation
Novo Nordisk Fonden (NNF13OC0004258)
National Institutes of Health
National Institute on Aging (R01AG048769)
National Institute of Neurological Disorders and Stroke (R01NS078304, R01NS078167, R01NS075177, NS075177, NS078304))
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD080573)
Topics: Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Keywords: glymphatic system, perivascular spaces, astrocytes, brain waste clearance, amyloid-beta, neurodegenerative diseases, traumatic brain injury, stroke, glymphatic dysfunction
MeSH terms: Aging, Animals, Astrocytes, Brain Injuries, Cerebrospinal Fluid, Humans, Lymphatic System

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The glymphatic system: a beginner's guide

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks