The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β
Open accessAbstract
Cerebrospinal fluid flows through channels around brain blood vessels that are bounded by astrocytic endfeet, mediated by water transport through aquaporin-4.
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In the citing paper
“the glymphatic system, a CSF–interstitial fluid transport pathway, supported by perivascular spaces, astrocytic water channels, vascular pulsatility, and meningeal lymphatic drainage, that contributes to waste clearance and fluid homeostasis in the brain (Iliff et al., 2012).”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Iliff et al., 2012
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Deletion of AQP4 channels reduces clearance of exogenous Aβ by 65%”
From Sleep Drives Metabolite Clearance from the Adult Brain (2013) · cites this paper as [12]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The glymphatic system uses the perivascular spaces as low-resistance routes for fast influx of CSF into deep brain regions1.”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [1]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The glymphatic system is a highly organized, brain-wide network for cerebrospinal fluid (CSF) transport that exports protein waste, including amyloid and tau1–3.”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [1]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Previous animal studies have shown communication between the subarachnoid cerebrospinal fluid (CSF) space and perivascular compartments of the brain (6-10) and spinal cord (11).”
From Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. (2018) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“In 2012, a brain-wide pathway for convective transport of waste solutes from the brain was first described and denoted the glymphatic system (7).”
From Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. (2018) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Impaired glymphatic function has been suggested to be instrumental in a range of brain diseases; this has been illustrated most in Alzheimer's dementia (7, 19, 20) but has also been shown to be relevant in posttraumatic encephalopathy (21), ageing (22), sleep (23, 24), depression (20), and exercise (25).”
From Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. (2018) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Moreover, animal studies report diverging findings regarding the sites of perivascular brain influx and efflux and direction of perivascular flow (7, 15, 16).”
From Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. (2018) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“and may thus be a determining factor for parenchymal tracer enrichment more than clearance, which has rather been proposed to be dependent on convective forces and AQP4 status in the glymphatic system (7).”
From Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. (2018) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“Clearance of MRI contrast agents, such as gadobutrol, has previously been proposed to potentially resemble clearance of brain macromolecules with similar properties (14), including amyloidβ (7) and tau (21, 66).”
From Brain-wide glymphatic enhancement and clearance in humans assessed with MRI. (2018) · cites this paper as [7]
The cited source says what the claim attributes to it.
In the citing paper
“For example, studies using injection of fluorescent tracers into cisterna magna of mice have suggested that paravascular circulation occurs via CSF convective flow through the ECS from the para-arterial to the paravenous spaces, which is regulated by AQP4 water channels on astrocytes, and therefore the system was renamed as the 'glymphatic' system (276, 293).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [276]
The cited source says what the claim attributes to it.
In the citing paper
“cerebrospinal fluid (CSF) recirculates through the brain, interchanging with interstitial fluid (ISF) and removing interstitial proteins, including Aβ (12, 13).”
From Sleep Drives Metabolite Clearance from the Adult Brain (2013) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“Influx of CSF is in part driven by arterial pulse waves that propel the movement of CSF inward along periarterial spaces (12).”
From Sleep Drives Metabolite Clearance from the Adult Brain (2013) · cites this paper as [12]
The cited source says what the claim attributes to it.
In the citing paper
“suggesting that convective movement of ISF is a substantial contributor to the removal of interstitial waste products and other products of cellular activity (12).”
From Sleep Drives Metabolite Clearance from the Adult Brain (2013) · cites this paper as [12]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“This mechanism is how curbing PCSK9 activity provides protection against the vascular aspects of Alzheimer’s pathology [33,77].”
From The Roles of PCSK9 in Alzheimer’s Disease: A Systematic Review of Clinical, Genetic, and Preclinical Evidence (2025) · cites this paper as [77]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Since it is difficult to control when rodents enter natural sleep, anesthesia is commonly used as a proxy for sleep1,24,99,100.”
From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [1]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“No statistical methods were used to predetermine sample sizes but our sample sizes are similar to those reported in previous publications3,4,12.”
From Brain clearance is reduced during sleep and anesthesia (2024) · cites this paper as [4]
Experimental — accuracy not yet measuredIn the citing paper
“The glymphatic system is a highly organized cerebrospinal fluid transport system that shares several key functions with the lymphatic vessels of peripheral tissues, including the export of excess interstitial fluid and proteins”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [24]
In the citing paper
“fluid transport through the glymphatic system is directionally polarized, with influx along penetrating arteries, fluid entry into the neuropil supported by AQP4, and efflux along the peri-venous spaces, as well as along the cranial and spinal nerves (24, 32–34).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [24]
In the citing paper
“Deletion of AQP4 channels reduces both the influx of CSF tracers and the efflux of solutes from the neuropil (24, 30, 31).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [24]
In the citing paper
“The polarized expression of the water channel, AQP4, in the vascular endfeet of astrocytes facilitates glymphatic fluid transport and amyloid-ß export in rodents (24, 30)(Fig. 1).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [24]
In the citing paper
“The motion of the brain is locally supplemented by the pulsatility of the penetrating arteries, as they enter the brain from the CSF-filled subarachnoid space, thereby driving CSF into the neuropil along the periarteral spaces (24).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [24]
In the citing paper
“The expression of aquaporin-4 (AQP4) in astrocytes significantly influences the transport and clearance functions of the glymphatic system.155”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [155]
In the citing paper
“It has previously been shown that neurotoxic molecules such as amyloid-β and tau are cleared from brain tissue along paravenous pathways (the glymphatic system)20”
From Cerebrospinal fluid tracer efflux to parasagittal dura in humans (2020) · cites this paper as [20]
In the citing paper
“Molecules from 0.8 to 70 kDa have been shown to penetrate the glia limitans to varying degrees, whereas molecules from 150 to 2000 kDa are confined within the perivascular space (18, 39, 40).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [40]
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Citations
Cites
Diffusion in Brain Extracellular Space
Syková, E., & Nicholson, C. (2008) · Physiological Reviews · doi:10.1152/physrev.00027.2007 · Cited by 1,481 · cited 5×
“1 nm, respectively (9)] pass the endfeet in a size- and structure-dependent manner (Fig.”
BackgroundInfluentialNielsen, S. M., Nagelhus, E. A., Amiry-Moghaddam, M. R., Bourque, C. W., Agre, P. C., & Ottersen, O. P. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-01-00171.1997 · Cited by 1,440
Self-citationReal-time imaging reveals the single steps of brain metastasis formation.
Kienast, Y., von Baumgarten, L., Fuhrmann, M., Klinkert, W. E. F., Goldbrunner, R., Herms, J., & Winkler, F. (2010) · Nature Medicine · doi:10.1038/nm.2072 · Cited by 1,138
Astrocyte-mediated control of cerebral blood flow
Takano, T., Tian, G.-F., Peng, W., Lou, N., Libionka, W., Han, X., & Nedergaard, M. (2005) · Nature Neuroscience · doi:10.1038/nn1623 · Cited by 1,137
Self-citationThree or more routes for leukocyte migration into the central nervous system
Ransohoff, R. M., Kivisäkk, P., & Kidd, G. (2003) · Nature Reviews Immunology · doi:10.1038/nri1130 · Cited by 1,052 · cited 1×
“Both lymphocytes and antigen-presenting cells in the subarachnoid CSF (49) may detect interstitial antigens delivered to the CSF by paravenous bulk outflow.”
BackgroundInterstitial-lymphatic mechanisms in the control of extracellular fluid volume
Aukland, K., & Reed, R. K. (1993) · Physiological Reviews · doi:10.1152/physrev.1993.73.1.1 · Cited by 938 · cited 1×
“The lymphatic vasculature represents a second circulation, parallel to the blood vasculature, that accounts for the clearance of interstitial fluid (ISF) with its constituent proteins and other solutes not absorbed across postcapillary venules (1, 2).”
BackgroundLehre, K. P., Levy, L., Ottersen, O. P., Storm‐Mathisen, J., & Danbolt, N. C. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-03-01835.1995 · Cited by 912
Mathiisen, T. M., Lehre, K. P., Danbolt, N. C., & Ottersen, O. (2010) · Glia · doi:10.1002/glia.20990 · Cited by 893
Neuronal activity regulates the regional vulnerability to amyloid-β deposition
Bero, A. W., Yan, P., Roh, J. H., Cirrito, J. R., Stewart, F. R., Raichle, M. E., Lee, J.-M., & Holtzman, D. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2801 · Cited by 880 · cited 1×
“AQP4 facilitates the para-vascular clearance of interstitial amyloid b Soluble amyloid b (Ab) is present in the interstitium of the healthy young brain, yet interstitial Ab levels are correlated with amyloid plaque burden (18).”
BackgroundEvidence for bulk flow of brain interstitial fluid: significance for physiology and pathology
Abbott, N. J. (2004) · Neurochemistry International · doi:10.1016/j.neuint.2003.11.006 · Cited by 786 · cited 5×
“Interstitial solutes have been thought to be cleared to the CSF by the convective bulk flow of ISF, which courses diffusely through brain tissue, rather than through an anatomically or functionally discrete structure (3, 4, 9).”
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Rudie, J. D., Rauschecker, A. M., Nabavizadeh, S. A., & Mohan, S. (2017) · Journal of Neuroimaging · doi:10.1111/jon.12493 · Cited by 105
Lee, S. H., Yoo, R., Choi, S. H., Oh, S., Ji, S., Lee, J., Huh, K. Y., Lee, J. Y., Hwang, I., Kang, K. M., et al. (2021) · Radiology · doi:10.1148/radiol.2021203784 · Cited by 109
The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment
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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
Decreased CSF clearance and increased brain amyloid in Alzheimer’s disease
Li, Y., Rusinek, H., Butler, T., Glodzik, L., Pirraglia, E., Babich, J. W., Mozley, P. D., Nehmeh, S. A., Pahlajani, S. S., Wang, X. H., et al. (2022) · Fluids and Barriers of the CNS · doi:10.1186/s12987-022-00318-y · Cited by 110
Kelley, D. H., & Thomas, J. H. (2022) · Annual Review of Fluid Mechanics · doi:10.1146/annurev-fluid-120720-011638 · Cited by 113
Xiong, Y., Chen, J., & Li, Y. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1125428 · Cited by 114
Delivery of oxytocin to the brain for the treatment of autism spectrum disorder by nasal application
Tanaka, A., Furubayashi, T., Arai, M., Inoue, D., Kimura, S., Kiriyama, A., Kusamori, K., Katsumi, H., Yutani, R., Sakane, T., et al. (2018) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.7b00991 · Cited by 104
Early neurovascular dysfunction in a transgenic rat model of Alzheimer’s disease
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Zhang, J., Zhan, Z., Li, X., Xing, A., Jiang, C., Chen, Y., Shi, W., & An, L. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00395 · Cited by 111
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“Markers circulating in CSF showed that the entry to GS was started in the parenchyma through a periarterial pathway surrounding the vascular smooth muscle cells bounded by the perivascular astrocytic endfeet [29].”
BackgroundInfluentialGlymphatic Cerebrospinal Fluid and Solute Transport Quantified by MRI and PET Imaging
Benveniste, H., Lee, H., Ozturk, B., Chen, X., Koundal, S., Vaska, P., Tannenbaum, A., & Volkow, N. D. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.11.014 · Cited by 106
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Tian, Y., Cai, X., Zhou, Y., Jin, A., Wang, S., Yang, Y., Mei, L., Jing, J., Li, S., Meng, X., et al. (2023) · Stroke and Vascular Neurology · doi:10.1136/svn-2022-002191 · Cited by 104
Contributions of glycogen to astrocytic energetics during brain activation
Dienel, G. A., & Cruz, N. F. (2014) · Metabolic Brain Disease · doi:10.1007/s11011-014-9493-8 · Cited by 105
Quintana, D. S., Westlye, L. T., Rustan, Ø. G., Tesli, N., Poppy, C. L., Smevik, H., Tesli, M., Røine, M., Mahmoud, R. A., Smerud, K. T., et al. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.93 · Cited by 103
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
Kogan, M. J., Aguirre, M. V., Morales-Zavala, F., Toledo, E. G., Guerrero, S., Giralt, E., & Araya, E. (2015) · International Journal of Nanomedicine · doi:10.2147/ijn.s82310 · Cited by 105
Non-Invasive MRI of Blood–Cerebrospinal Fluid Barrier Function
Evans, P., Sokolska, M., Alves, A., Harrison, I. F., Ohene, Y., Nahavandi, P., Ismail, O., Miranda, E., Lythgoe, M. F., Thomas, D. L., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16002-4 · Cited by 122
Huang, J., van Zijl, P. C. M., Han, X., Dong, C. M., Cheng, G. W., Tse, K., Knutsson, L., Chen, L., Lai, J. H. C., Wu, E. X., et al. (2020) · Science Advances · doi:10.1126/sciadv.aba3884 · Cited by 103
Cerebral Vessels: An Overview of Anatomy, Physiology, and Role in the Drainage of Fluids and Solutes
Agarwal, N., & Carare, R. O. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.611485 · Cited by 119
“In the past decade, multiple waste clearance pathways have been characterized in the brain: the glymphatic pathway, intramural periarterial drainage pathway (IPAD), flow along cranial nerves, and meningeal lymphatics along the dural venous sinuses (6, 39, 47), still extensively debated (48, 49).”
BackgroundA 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
“4A), similar to how the glymphatic system is proposed to increase convective CSF bulk flow ( 35 ).”
Salehpour, F., Khademi, M., Bragin, D. E., & DiDuro, J. O. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23062975 · Cited by 106
Mitra, S., Anjum, J., Muni, M., Das, R. C., Rauf, A., Islam, F., Emran, T. B., Semwal, P., Hemeg, H. A., Alhumaydhi, F. A., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112877 · Cited by 106
Clearance from the mouse brain by convection of interstitial fluid towards the ventricular system
Bedussi, B., van Lier, M. G. J. T. B., Bartstra, J. W., de Vos, J., Siebes, M., VanBavel, E., & Bakker, E. N. T. P. (2015) · Fluids and Barriers of the CNS · doi:10.1186/s12987-015-0019-5 · Cited by 102
Impaired brain glymphatic flow in experimental hepatic encephalopathy
Hadjihambi, A., Harrison, I. F., Costas‐Rodríguez, M., Vanhaecke, F., Arias, N., Gallego‐Durán, R., Mastitskaya, S., Hosford, P. S., Damink, S. W. M. O., Davies, N. A., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.08.021 · Cited by 105
Christensen, J., Yamakawa, G. R., Shultz, S. R., & Mychasiuk, R. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101917 · Cited by 110
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
“…and chronic traumatic encephalopathy, suggesting its involvement in virtually most neurodegenerative diseases (Iliff et al., 2012; Arbel-Ornath et al., 2013; Rangroo Thrane et al., 2013; Jessen et al., 2015; Plog et al., 2015; Louveau et al., 2016; Jiang et al., 2017; Mestre et al., 2018b, 2020a).”
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Bottigliengo, D., Foco, L., Seibler, P., Klein, C., König, I. R., & Fabiola Del Greco, M. (2022) · Brain · doi:10.1093/brain/awac193 · Cited by 104
Blood–brain barrier and blood–cerebrospinal fluid barrier in normal and pathological conditions
Ueno, M., Chiba, Y., Murakami, R., Matsumoto, K., Kawauchi, M., & Fujihara, R. (2016) · Brain Tumor Pathology · doi:10.1007/s10014-016-0255-7 · Cited by 106
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
Taoka, T., & Naganawa, S. (2018) · Magnetic Resonance in Medical Sciences · doi:10.2463/mrms.rev.2017-0116 · Cited by 104
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
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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
Solar, P., Zamani, A., Lakatosová, K., & Joukal, M. (2022) · Fluids and Barriers of the CNS · doi:10.1186/s12987-022-00312-4 · Cited by 103
Brain perivascular macrophages: Recent advances and implications in health and diseases
Yang, T., Guo, R., & Zhang, F. (2019) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13263 · Cited by 97
Diagnosing and Treating Depression in Patients with Alzheimer’s Disease
Burke, A. D., Goldfarb, D., Bollam, P., & Khokher, S. (2019) · Neurology and Therapy · doi:10.1007/s40120-019-00148-5 · Cited by 115
Afferent and efferent immunological pathways of the brain. Anatomy, Function and Failure
Carare, R. O., Hawkes, C. A., & Weller, R. O. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.10.012 · Cited by 100
Review of ‘the Potential Role of Arterial Stiffness in the Pathogenesis of Alzheimer’s Disease’
Hughes, T. M., Craft, S., & López, O. L. (2015) · Neurodegenerative Disease Management · doi:10.2217/nmt.14.53 · Cited by 105
Human and mouse cortical astrocytes differ in aquaporin-4 polarization toward microvessels
Eidsvaag, V. A., Enger, R., Hansson, H., Eide, P. K., & Nagelhus, E. A. (2017) · Glia · doi:10.1002/glia.23138 · Cited by 100
Self-citationSmith, A. J., Duan, T., & Verkman, A. S. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0728-0 · Cited by 102
Intrathecal Use of Gadobutrol for Glymphatic MR Imaging: Prospective Safety Study of 100 Patients
Edeklev, C. S., Halvorsen, M., Løvland, G., Vatnehol, S. A. S., Gjertsen, Ø., Nedregaard, B., Sletteberg, R., Ringstad, G. A., & Eide, P. K. (2019) · American Journal of Neuroradiology · doi:10.3174/ajnr.a6136 · Cited by 100
The glymphatic system and meningeal lymphatics of the brain: new understanding of brain clearance
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“The first attempt to study the issue was the glymphatic system theory (Iliff et al. 2012; Jessen et al. 2015).”
BackgroundMethodInfluentialWagner, K., Unger, L., Salman, M. M., Kitchen, P., Bill, R. M., & Yool, A. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031388 · Cited by 97
Gao, J., Song, Q., Gu, X. Q., Jiang, G., Huang, J., Tang, Y., Yu, R., Wang, A., Huang, Y., Zheng, G., et al. (2023) · Nature Nanotechnology · doi:10.1038/s41565-023-01551-8 · Cited by 101
“…NPs high-density lipoprotein (rHDL) and poly(ethylene glycol)- b -poly(lactic acid) (PEG-PLA) NPs, are cleared fairly rapidly (half-life, 5 h) from the mouse brain through the paravascular glymphatic pathway 26 , which is a waste clearance system for interstitial solute brain clearance 27,28 .”
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Endothelial Dysfunction in Neurodegenerative Diseases
Fang, Y., Hsieh, Y., Hu, C., & Tu, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032909 · Cited by 102
Mendes, A. J., Ribaldi, F., Lathuilière, A., Ashton, N. J., Janelidze, S., Zetterberg, H., Scheffler, M., Assal, F., Garibotto, V., Blennow, K., et al. (2024) · Journal of Neurology · doi:10.1007/s00415-023-12148-5 · Cited by 112
“The advantage of CSF over plasma could be due to the fact that CSF surrounds the brain parenchyma directly and functions as a drainage system for brain extracellular solutes [43].”
Phosphodiesterase III inhibitor promotes drainage of cerebrovascular β‐amyloid
Maki, T., Okamoto, Y., Carare, R. O., Hase, Y., Hattori, Y., Hawkes, C. A., Saitô, S., Yamamoto, Y., Terasaki, Y., Ishibashi‐Ueda, H., et al. (2014) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.79 · Cited by 101
Potential Pathways for CNS Drug Delivery Across the Blood-Cerebrospinal Fluid Barrier
Strazielle, N., & Ghersi‐Egea, J. (2016) · Current Pharmaceutical Design · doi:10.2174/1381612822666160726112115 · Cited by 104
Measuring Glymphatic Flow in Man Using Quantitative Contrast-Enhanced MRI
Watts, R., Steinklein, J. M., Waldman, L. E., Zhou, X., & Filippi, C. G. (2019) · American Journal of Neuroradiology · doi:10.3174/ajnr.a5931 · Cited by 96
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
Xie, Y., Ba, L., Wang, M., Deng, S., Chen, S., Huang, L., Zhang, M., Wang, W., & Ding, F. (2019) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13218 · Cited by 102
Self-citationThe Blood–Brain Barrier and Its Intercellular Junctions in Age-Related Brain Disorders
Costea, L., Mészáros, Á., Bauer, H., Bauer, H., Traweger, A., Wilhelm, I., Farkas, A. E., & Krizbai, I. A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215472 · Cited by 102
“This flow was shown to contribute to the clearance of extracellular proteins and metabolic waste products through the newly rediscovered glymphatic system [13,14].”
BackgroundIverson, G. L., Gardner, A. J., Shultz, S. R., Solomon, G. S., McCrory, P. R., ZAFONTE, R. D., Perry, G. L., Hazrati, L., Keene, C. D., & Castellani, R. J. (2019) · Brain · doi:10.1093/brain/awz286 · Cited by 105
“The glymphatic system (Iliff et al., 2012, 2013) is believed to be a brain-wide perivascular pathway that supports the clearance and removal of interstitial solutes from the brain, including amyloid-b and tau, especially during sleep (Boespflug and Iliff, 2018).”
BackgroundLi, G., Cao, Y., Tang, X., Huang, J., Cai, L., & Zhou, L. (2022) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x221098145 · Cited by 103
Astrocytes in the regulation of cerebrovascular functions
Cohen‐Salmon, M., Slaoui, L., Mazaré, N., Gilbert, A., Oudart, M., Alvear‐Perez, R., Elorza‐Vidal, X., Chever, O., & Boulay, A. (2021) · Glia · doi:10.1002/glia.23924 · Cited by 93
“In the glymphatic model, influx is periarterial and the efflux is perivenous (Iliff et al., 2012).”
BackgroundInfluentialPapisov, M. I., Belov, V. V., & Gannon, K. S. (2013) · Molecular Pharmaceutics · doi:10.1021/mp300474m · Cited by 97
A new look at cerebrospinal fluid movement
Orešković, D., & Klarica, M. (2014) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-11-16 · Cited by 104
Magnetic Resonance Imaging of Normal Pressure Hydrocephalus
Bradley, W. G. (2016) · Seminars in Ultrasound CT and MRI · doi:10.1053/j.sult.2016.01.005 · Cited by 97
Aquaporins in Brain Edema and Neuropathological Conditions
Filippidis, A., Carozza, R. B., & Rekate, H. L. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms18010055 · Cited by 96
Pirici, I., Balsanu, T. A., Cătălin, B., Mărgăritescu, C., Divan, T., Văcăraș, V., Mogoantă, L., Pirici, D. N., Carare, R. O., & Muresanu, D. F. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms19010046 · Cited by 100
Huibregtse, M. E., Bazarian, J. J., Shultz, S. R., & Kawata, K. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.08.029 · Cited by 100
“The glymphatic clearance pathway is characterized by para-arterial influx of CSF from the subarachnoid space into the interstitial space, followed by a paravenous efflux of interstitial fluid (ISF) from the brain parenchyma, where neural factors travel through the dural venous sinuses and drain into the cervical lymph…”
BackgroundMassey, A., Boag, M. K., Magnier, A., Bispo, D. P. C. F., Khoo, T. K., & Pountney, D. L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112928 · Cited by 103
Glymphatic system: an emerging therapeutic approach for neurological disorders
Gao, Y., Liu, K., & Zhu, J. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1138769 · Cited by 109
“…has been proved to have crucial effect on protein clearance, such as amyloid β (Aβ), α-synuclein and other proteins, which are involved in the pathogenesis of AD, PD and other neurodegenerative diseases (Iliff et al., 2012; Jucker and Walker, 2013; Xu et al., 2015; Da Mesquita et al., 2018).”
BackgroundInfluentialZhang, L., Chopp, M., Zhang, Y., Xiong, Y., Li, C., Sadry, N., Rhaleb, I. A., Lü, M., & Zhang, Z. G. (2016) · Stroke · doi:10.1161/strokeaha.115.012578 · Cited by 98
Maugeri, R., Schiera, G., Liegro, C. M. D., Fricano, A., Iacopino, D. G., & Liegro, I. D. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17071029 · Cited by 97
Begum, G., Song, S., Wang, S., Zhao, H., Bhuiyan, M. I. H., Li, E., Nepomuceno, R., Ye, Q., Sun, M., Calderon, M. J., et al. (2017) · Glia · doi:10.1002/glia.23232 · Cited by 100
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
Bower, D. V., Richter, J. K., von Tengg‐Kobligk, H., Heverhagen, J. T., & Runge, V. M. (2019) · Investigative Radiology · doi:10.1097/rli.0000000000000567 · Cited by 96
Piantino, J. A., Lim, M. M., Newgard, C. D., & Iliff, J. J. (2019) · Current Pain and Headache Reports · doi:10.1007/s11916-019-0799-4 · Cited by 98
Self-citationImmune dynamics in the CNS and its barriers during homeostasis and disease*
Buckley, M. W., & McGavern, D. B. (2022) · Immunological Reviews · doi:10.1111/imr.13066 · Cited by 107
Involvement of Aquaporin 4 in Astrocyte Function and Neuropsychiatric Disorders
Xiao, M., & Hu, G. (2014) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12267 · Cited by 99
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
Boespflug, E. L., Simon, M. J., Leonard, E., Grafe, M. R., Woltjer, R. L., Silbert, L. C., Kaye, J. A., & Iliff, J. J. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180367 · Cited by 100
Self-citationThe current state of immunotherapy for gliomas: an eye toward the future
Fecci, P. E., & Sampson, J. H. (2019) · Journal of neurosurgery · doi:10.3171/2019.5.jns181762 · Cited by 95
Echagarruga, C., Gheres, K. W., Norwood, J. N., & Drew, P. J. (2020) · eLife · doi:10.7554/elife.60533 · Cited by 99
“DOI: https://doi.org/10.7554/eLife.60533 16 of 39 penetrating arterioles are surrounded by a thin paravascular space (Iliff et al., 2012) filled with collagen fibers tethering the artery to the brain (Roggendorf and Cervós-Navarro, 1977).”
BackgroundInfluentialMestre, H., Verma, N., Greene, T. D., Lin, L. A., Ladrón-de-Guevara, A., Sweeney, A. M., Liu, G., Thomas, V. K., Galloway, C. A., Bentley, K. L. D. M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31257-9 · Cited by 97
Self-citationIs Vasomotion in Cerebral Arteries Impaired in Alzheimer’s Disease?
Marco, L. Y. D., Farkas, E., Martin, C. J., Venneri, A., & Frangi, A. F. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142976 · Cited by 94
Wang, H., Yang, B., Qiu, L., Yang, C., Kramer, J. A., Su, Q., Guo, Y., Brown, R. H., Gao, G., & Xu, Z. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt454 · Cited by 99
Functional deficits induced by cortical microinfarcts
Summers, P. M., Hartmann, D. A., Hui, E. S. K., Nie, X., Deardorff, R. L., McKinnon, E. T., Helpern, J. A., Jensen, J. H., & Shih, A. Y. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16685573 · Cited by 96
Engineering challenges for brain tumor immunotherapy
Lyon, J. G., Mokarram, N., Saxena, T. K., Carroll, S. L., & Bellamkonda, R. V. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2017.06.006 · Cited by 102
From Cerebrospinal Fluid to Blood: The Third Wave of Fluid Biomarkers for Alzheimer’s Disease
Zetterberg, H., & Blennow, K. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179926 · Cited by 98
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
Reid, M. J., Beltran-Lobo, P., Johnson, L., Perez‐Nievas, B. G., & Noble, W. J. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.572850 · Cited by 98
Structural, Functional, and Molecular Imaging of Autism Spectrum Disorder
Li, X., Zhang, K., He, X., Zhou, J., Jin, C., Shen, L., Gao, Y., Tian, M., & Zhang, H. (2021) · Neuroscience Bulletin · doi:10.1007/s12264-021-00673-0 · Cited by 94
Falcone, J. A., Salameh, T. S., Yi, X., Cordy, B., Mortell, W. G., Kabanov, A. V., & Banks, W. A. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.216705 · Cited by 100
Kandel, B. M., Avants, B., Gee, J. C., McMillan, C. T., Erus, G., Doshi, J. J., Davatzikos, C. A., Wolk, D. A., & Initiative, A. D. N. (2016) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2016.03.001 · Cited by 98
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
Stress and aging act through common mechanisms to elicit neuroinflammatory priming
Fonken, L. K., Frank, M. G., Gaudet, A. D., & Maier, S. F. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.07.012 · Cited by 98
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
Valnes, L. M., Mitusch, S. K., Ringstad, G. A., Eide, P. K., Funke, S. W., & Mardal, K. (2020) · Scientific Reports · doi:10.1038/s41598-020-66042-5 · Cited by 94
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
“The glymphatic pathway is mainly dependent on the AQP4 water channel, a protein found on astrocyte end feet that is involved in the fluid flow of CSF along the arterial perivascular space, where it mixes into the ISF and exits through perivenous space [42–44].”
BackgroundInfluentialImpaired 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
“The PVS direction is also perpendicular to the direction of both the projection fibers (mostly in the z-axis) and the association fibers (mostly in the y-axis).”
BackgroundInfluentialCerebrospinal Fluid–Basic Concepts Review
Czarniak, N., Kamińska, J., Matowicka-Karna, J., & Koper‐Lenkiewicz, O. M. (2023) · Biomedicines · doi:10.3390/biomedicines11051461 · Cited by 110
(2020) · International Review of Neurobiology · doi:10.1016/bs.irn.2020.02.006 · Cited by 87
Self-citation
Metadata
- Authors
- 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., Nagelhus, E. A., & Nedergaard, M.
- Affiliations
- University of Rochester Medicine (US)
- University of Oslo (NO)
- Stony Brook University (US)
- Corresponding author
- Iliff, Jeffrey J.
- Nedergaard, Maiken
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2012-08-15
- Volume
- 4
- Issue
- 147
- Pages
- 147ra111-147ra111
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- PMC
- PMC3551275
- OpenAlex
- W2167183660
- Cited by
- 5,824
- References
- 56
- Citations by year
- 2026: 871 · 2025: 767 · 2024: 669 · 2023: 605 · 2022: 546 · 2021: 456 · 2020: 400 · 2019: 358 · 2018: 281 · 2017: 279 · 2016: 203 · 2015: 160 · 2014: 128 · 2013: 83 · 2012: 13
- FWCI
- 50.61
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS078304, R01NS078167, R01NS075177, R01NS075345, R01NS052534)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- cerebrospinal fluid flow, interstitial fluid clearance, amyloid-beta clearance, aquaporin-4, astrocytes, Alzheimer's disease, neurodegeneration
- MeSH terms
- Animals, Astrocytes, Biological Transport, Brain, Cerebral Ventricles, Cerebrospinal Fluid, Male, Mice, Inbred C57BL, Water, Amyloid beta-Peptides, Imaging, Three-Dimensional, Microscopy, Fluorescence, Multiphoton, Extracellular Fluid, Mice, Aquaporin 4
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