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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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Filiano, A. J., Gadani, S. P., & Kipnis, J. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.39 · Cited by 199
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Erickson, M. A., & Banks, W. A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071632 · Cited by 203
Wang, M., Ding, F., Deng, S., Guo, X., Wang, W., Iliff, J. J., & Nedergaard, M. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2112-16.2017 · Cited by 199
Self-citationConserved meningeal lymphatic drainage circuits in mice and humans
Jacob, L., Brito, J. M., Lenck, S., Corcy, C., Benbelkacem, F., Geraldo, L. H., Xu, Y., Thomas, J.-M., Kamouh, M.-R. E., Spajer, M., et al. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20220035 · Cited by 206
“By bridging the CNS with the peripheral immune system, MLVs control both brain waste clearance and neuroimmune communication.”
BackgroundInfluentialRamanathan, A., Nelson, A. R., Sagare, A. P., & Zlokovic, B. V. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00136 · Cited by 205
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Chong, P. L. H., Garic, D., Shen, M. D., Lundgaard, I., & Schwichtenberg, A. J. (2021) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2021.101572 · Cited by 208
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Myung, J., Schmal, C., Hong, S., Tsukizawa, Y., Rose, P., Zhang, Y., Holtzman, M. J., Schutter, E. D., Herzel, H., Bordyugov, G., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03507-2 · Cited by 193
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Dorrier, C., Jones, H. E., Pintarić, L., Siegenthaler, J. A., & Daneman, R. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00525-w · Cited by 204
Chen, T., Dai, Y., Hu, C., Lin, Z., Wang, S., Yang, J., Zeng, L., Li, S., & Li, W. (2024) · Fluids and Barriers of the CNS · doi:10.1186/s12987-024-00557-1 · Cited by 205
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“The fourth lymphatic pathway is the paravascular space which is a narrow space between the irregular surface of the leptomeningeal and the outer basement membrane of the vessel walls and that of the glia endfeet [32, 33], and it has been proposed to be part of the glymphatic pathway [34].”
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Croese, T., Castellani, G., & Schwartz, M. (2021) · Nature Immunology · doi:10.1038/s41590-021-00994-2 · Cited by 197
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Gakuba, C., Gaberel, T., Goursaud, S., Bourges, J., Di Palma, C., Quenault, A., de Lizarrondo, S. M., Vivien, D., & Gauberti, M. (2018) · Theranostics · doi:10.7150/thno.19154 · Cited by 190
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Shen, X.-Y., Gao, Z.-K., Han, Y., Yuan, M., Guo, Y., & Bi, X. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.755955 · Cited by 198
“Under normal physiological conditions, astrocytes can isolate and protect the CNS (Iliff et al., 2012; Nedergaard, 2013).”
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Kurz, C., Walker, L., Rauchmann, B., & Perneczky, R. (2022) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12782 · Cited by 183
Implications of the discovery of brain lymphatic pathways
Iliff, J. J., Goldman, S. A., & Nedergaard, M. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00221-5 · Cited by 188
Self-citationChen, H.-L., Chen, P.-C., Lu, C.-H., Tsai, N., Yu, C.-C., Chou, K., Lai, Y., Taoka, T., & Lin, W. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/4034509 · Cited by 182
“coupled by interstitial bulk flow supported by astrocytic AQP4 water channels [4].”
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Sosunov, A. A., Wu, X., Tsankova, N. M., Guilfoyle, E., McKhann, G. M., & Goldman, J. E. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.4037-13.2014 · Cited by 185
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Verkman, A. S., Smith, A. J., Phuan, P., Tradtrantip, L., & Anderson, M. O. (2017) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2017.1398236 · Cited by 196
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Boire, A., Brandsma, D., Brastianos, P. K., Le Rhun, E., Ahluwalia, M., Junck, L., Glantz, M., Groves, M. D., Lee, E. Q., Lin, N., et al. (2019) · Neuro-Oncology · doi:10.1093/neuonc/noz012 · Cited by 183
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Raper, D. M. S., Louveau, A., & Kipnis, J. (2016) · Trends in Neurosciences · doi:10.1016/j.tins.2016.07.001 · Cited by 184
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Bedussi, B., Almasian, M., de Vos, J., VanBavel, E., & Bakker, E. N. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17737984 · Cited by 181
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Self-citationSteward, C. E., Venkatraman, V. K., LUI, E. H., Malpas, C. B., Ellis, K. A., Cyarto, E., Vivash, L. E., O'Brien, T. J., Velakoulis, D., Ames, D. J., et al. (2021) · Journal of Neuroimaging · doi:10.1111/jon.12837 · Cited by 184
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Yıldız, S., Thyagaraj, S., Jin, N., Zhong, X., Pahlavian, S. H., Martin, B. A., Loth, F., Oshinski, J. N., & Sabra, K. G. (2017) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.25591 · Cited by 178
Louveau, A., Mesquita, S. D., & Kipnis, J. (2016) · Neuron · doi:10.1016/j.neuron.2016.08.027 · Cited by 177
Siow, T. Y., Toh, C., Hsu, J., Liu, G.-H., Lee, S., Chen, N., Fu, C. J., Castillo, M., & Fang, J. (2021) · Neurology · doi:10.1212/wnl.0000000000013215 · Cited by 179
“The discovery of the glymphatic system led to a new perspective into brain protein homeostasis and offers a promising target for the prevention or therapeutics of neurodegenerative diseases.(1,2) This highly organized fluid transport system involves CSF inflow along the arterial perivascular spaces (PVS) and transfer…”
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Da Mesquita, S., Herz, J., Wall, M., Dykstra, T., de Lima, K. A., Norris, G. T., Dabhi, N., Kennedy, T., Baker, W., & Kipnis, J. (2021) · Science Advances · doi:10.1126/sciadv.abe4601 · Cited by 172
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“No statistical methods were used to predetermine sample sizes but our sample sizes are similar to those reported in previous publications 3,4,12 .”
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Alzheimer's Disease Puzzle: Delving into Pathogenesis Hypotheses
(2024) · aging and disease · doi:10.14336/ad.2023.0608 · Cited by 183
Gomolka, R. S., Hablitz, L. M., Mestre, H., Giannetto, M. J., Du, T., Hauglund, N. L., Xie, L., Peng, W., Martinez, P. M., Nedergaard, M., et al. (2023) · eLife · doi:10.7554/elife.82232 · Cited by 188
“In contrast to prior report (15), but consistent with the glymphatic model where ventricular fluid dynamics are upstream of 89 cisterna magna injections (19), no differences in the tracer distribution were found in the ventricular systems.”
BackgroundMethodResultInfluentialSelf-citationMultiphoton fluorescence microscopy for in vivo imaging
Xu, C., Nedergaard, M., Fowell, D. J., Friedl, P., & Ji, N. (2024) · Cell · doi:10.1016/j.cell.2024.07.036 · Cited by 182
Self-citationCerebral Edema in Traumatic Brain Injury
Winkler, E. A., Minter, D. J., Yue, J. K., & Manley, G. T. (2016) · Neurosurgery Clinics of North America · doi:10.1016/j.nec.2016.05.008 · Cited by 177
Boespflug, E. L., & Iliff, J. J. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.11.031 · Cited by 179
Self-citationMicrogravity-Induced Fluid Shift and Ophthalmic Changes
Nelson, E. S., Mulugeta, L., & Myers, J. G. (2014) · Life · doi:10.3390/life4040621 · Cited by 176
Drainage of Cells and Soluble Antigen from the CNS to Regional Lymph Nodes
Laman, J. D., & Weller, R. O. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9470-8 · Cited by 168
It's complicated: The relationship between sleep and Alzheimer's disease in humans
Lucey, B. P. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105031 · Cited by 172
Multicellular Self-Assembled Spheroidal Model of the Blood Brain Barrier
Urich, E., Patsch, C., Aigner, S., Graf, M. R., Iacone, R., & Freskgård, P. (2013) · Scientific Reports · doi:10.1038/srep01500 · Cited by 170
Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus
Wang, Z., Zhang, Y., Hu, F., Ding, J., & Wang, X. (2020) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13526 · Cited by 173
Host Immune Response to Infection and Cancer: Unexpected Commonalities
Goldszmid, R. S., Dzutsev, A., & Trinchieri, G. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.02.003 · Cited by 172
Gandhi, J., Antonelli, A. C., Afridi, A., Vatsia, S. K., Joshi, G. S., Romanov, V., Murray, I. V. J., & Khan, S. A. (2019) · Reviews in the Neurosciences · doi:10.1515/revneuro-2016-0035 · Cited by 171
Jurisch‐Yaksi, N., Yaksi, E., & Kızıl, Ç. (2020) · Glia · doi:10.1002/glia.23849 · Cited by 174
Failure of Perivascular Drainage of β‐amyloid in Cerebral Amyloid Angiopathy
Hawkes, C. A., Jayakody, N., Johnston, D. A., Bechmann, I., & Carare, R. O. (2014) · Brain Pathology · doi:10.1111/bpa.12159 · Cited by 170
Energy Metabolism Decline in the Aging Brain—Pathogenesis of Neurodegenerative Disorders
Błaszczyk, J. W. (2020) · Metabolites · doi:10.3390/metabo10110450 · Cited by 166
“The circulation of blood and cerebrospinal fluid supply the brain with oxygen, glucose, and nutrients necessary for the life and functioning of neurons [124,125].”
BackgroundBreaking through the basement membrane barrier to improve nanotherapeutic delivery to tumours
Wang, Q., Liang, Q., Dou, J., Zhou, H., Zeng, C., Pan, H., Shen, Y., Li, Q., Liu, Y., Leong, D. T., et al. (2023) · Nature Nanotechnology · doi:10.1038/s41565-023-01498-w · Cited by 167
“5) 26 .”
Toward a conceptual framework for early brain and behavior development in autism
Piven, J., Elison, J. T., & Zylka, M. J. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.131 · Cited by 173
Bacyinski, A., Xu, M., Wang, W., & Hu, J. (2017) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2017.00101 · Cited by 170
Yokota, H., Vijayasarathi, A., Cekic, M. M., Hirata, Y., Linetsky, M., Ho, M. J., Kim, W. B., & Salamon, N. (2019) · Current Gerontology and Geriatrics Research · doi:10.1155/2019/5675014 · Cited by 162
Luo, A., Xie, Z., Wang, Y., Wang, X., Li, S., Yan, J., Zhan, G., Zhou, Z., Zhao, Y., & Li, S. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104642 · Cited by 169
Østergaard, L., Aamand, R., Karabegovic, S., Tietze, A., Blicher, J. U., Mikkelsen, I. K., Iversen, N., Secher, N., Engedal, T. S., Anzabi, M., et al. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.173 · Cited by 160
Ramirez, J., Berezuk, C., McNeely, A. A., Gao, F., McLaurin, J., & Black, S. E. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-016-0343-6 · Cited by 164
Park, J., Aryal, M., Vykhodtseva, N. I., Zhang, Y., & McDannold, N. J. (2016) · Journal of Controlled Release · doi:10.1016/j.jconrel.2016.10.011 · Cited by 162
Zheng, Z., Li, D., Liu, Z., Peng, H., Sung, H. H. Y., Kwok, R. T. K., Williams, I. D., Lam, J. W. Y., Qian, J., & Tang, B. Z. (2019) · Advanced Materials · doi:10.1002/adma.201904799 · Cited by 161
Han, F., Chen, J., Belkin-Rosen, A., Gu, Y., Luo, L., Buxton, O. M., Liu, X., & Initiative, A. D. N. (2021) · PLoS Biology · doi:10.1371/journal.pbio.3001233 · Cited by 170
Potentiating glymphatic drainage minimizes post-traumatic cerebral oedema
Hussain, R., Tithof, J., Wang, W., Cheetham-West, A., Song, W., Peng, W., Sigurdsson, B., Kim, D., Sun, Q., Peng, S., et al. (2023) · Nature · doi:10.1038/s41586-023-06737-7 · Cited by 169
“Under physiological conditions, CSF is partially or fully drained by outflow pathways that include the meningeal and cervical lymphatic vessels 15,16 , which return fluid through the thoracic duct to the venous circulation 14,17 .”
BackgroundSelf-citationGouveia-Freitas, K., & de Bastos-Leite, A. J. (2021) · Neuroradiology · doi:10.1007/s00234-021-02718-7 · Cited by 166
Neuropathobiology of COVID-19: The Role for Glia
Tremblay, M.-E., Madore, C., Bordeleau, M., Tian, L., & Verkhratsky, A. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.592214 · Cited by 159
“Furthermore, the astroglia-based glymphatic waste collection system (Iliff et al., 2012) declines with age, which affects clearance of numerous by-products and toxic substances (Kress et al., 2014).”
BackgroundGadolinium deposition in the brain
Kanda, T., Nakai, Y., Oba, H., Toyoda, K., Kitajima, K., & Furui, S. (2016) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2016.08.024 · Cited by 164
Cerebral small vessel disease: neuroimaging markers and clinical implication
Chen, X., Wang, J., Shan, Y., Cai, W., Liu, S., Hu, M., Liao, S., Huang, X., Zhang, B., Wang, Y., et al. (2018) · Journal of Neurology · doi:10.1007/s00415-018-9077-3 · Cited by 166
Extracellular Interactions of Alpha-Synuclein in Multiple System Atrophy
Valdinocci, D., Radford, R. A. W., Goulding, M., Hayashi, J., Chung, R. S., & Pountney, D. L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19124129 · Cited by 161
Analysis of convective and diffusive transport in the brain interstitium
Ray, L., Iliff, J. J., & Heys, J. J. (2019) · Fluids and Barriers of the CNS · doi:10.1186/s12987-019-0126-9 · Cited by 167
Self-citationDexmedetomidine enhances glymphatic brain delivery of intrathecally administered drugs
Lilius, T. O., Blomqvist, K. J., Hauglund, N. L., Liu, G., Stæger, F. F., Bærentzen, S. L., Du, T., Ahlström, F. H. G., Backman, J. T., Kalso, E. A., et al. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.05.005 · Cited by 159
Self-citationCells of the Blood–Brain Barrier: An Overview of the Neurovascular Unit in Health and Disease
McConnell, H., & Mishra, A. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2289-6_1 · Cited by 174
Toward more predictive genetic mouse models of Alzheimer’s disease
Onos, K. D., Sukoff Rizzo, S. J., Howell, G. R., & Sasner, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2015.12.003 · Cited by 156
Ashraf, A., Clark, M., & So, P. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00065 · Cited by 163
Xia, M., Yang, L., Sun, G., Qi, S., & Li, B. (2017) · Psychopharmacology · doi:10.1007/s00213-016-4473-9 · Cited by 149
Translational value of choroid plexus imaging for tracking neuroinflammation in mice and humans
Fleischer, V., Gonzalez-Escamilla, G., Ciolac, D., Albrecht, P., Küry, P., Gruchot, J., Dietrich, M., Hecker, C., Müntefering, T., Bock, S., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2025000118 · Cited by 152
“The ChP plays an essential role in CSF production and brain waste clearance pathways, including the recently discovered glymphatic transport of CSF along the periarterial spaces (2 – 4).”
Smith, A. J., & Verkman, A. S. (2017) · The FASEB Journal · doi:10.1096/fj.201700999 · Cited by 162
Biology of adeno-associated viral vectors in the central nervous system
Murlidharan, G., Samulski, R. J., & Asokan, A. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00076 · Cited by 174
Structure and Junctional Complexes of Endothelial, Epithelial and Glial Brain Barriers
Dias, M. C., Mapunda, J. A., Vladymyrov, M., & Engelhardt, B. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215372 · Cited by 163
Recent advances in the modeling of Alzheimer’s disease
Sasaguri, H., Hashimoto, S., Watamura, N., Sato, K., Takamura, R., Nagata, K., Tsubuki, S., Ohshima, T., Yoshiki, A., Sato, K., et al. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.807473 · Cited by 157
Baker, G. J., Yadav, V. N., Motsch, S., Koschmann, C. J., Calinescu, A., Mineharu, Y., Camelo-Piragua, S. I., Orringer, D. A., Bannykh, S., Nichols, W. S., et al. (2014) · Neoplasia · doi:10.1016/j.neo.2014.06.003 · Cited by 163
Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances
Jiang, Q., Liu, J., Huang, S., Wang, X.-Y., Chen, X., Liu, G.-H., Ye, K., Song, W., Masters, C. L., Wang, J., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02145-7 · Cited by 165
Samaranch, L., Salegio, E. A., Sebastián, W. S., Kells, A. P., Bringas, J. R., Forsayeth, J., & Bankiewicz, K. S. (2013) · Human Gene Therapy · doi:10.1089/hum.2013.005 · Cited by 158
Oxyphor 2P: A High-Performance Probe for Deep-Tissue Longitudinal Oxygen Imaging
Esipova, T. V., Barrett, M. J. P., Erlebach, E., Masunov, A. E., Weber, B., & Vinogradov, S. A. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.12.022 · Cited by 162
Oksanen, M., Lehtonen, Š., Jaronen, M., Goldsteins, G., Hämäläinen, R. H., & Koıstınaho, J. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03111-7 · Cited by 166
Sundaram, S., Hughes, R. L., Peterson, E., Müller-Oehring, E. M., Brontë-Stewart, H. M., Poston, K. L., Faerman, A., Bhowmick, C., & Schulte, T. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.05.016 · Cited by 152
Venkat, P., Chopp, M., & Chen, J. (2017) · Journal of the American Heart Association · doi:10.1161/jaha.117.005819 · Cited by 165
Fluid dynamics of cerebrospinal fluid flow in perivascular spaces
Thomas, J. H. (2019) · Journal of The Royal Society Interface · doi:10.1098/rsif.2019.0572 · Cited by 155
“The model can also include a flow ofwater across porous ductwalls into a space corresponding to the parenchyma, representing the exchange ofwater (but not all solvents) through aquaporin-4 channels between CSF in a PVS and interstitial fluid (ISF) in the parenchyma, and a flow of ISF through the parenchyma, in accord…”
ResultMechanisms of Astrocyte-Mediated Cerebral Edema
Stokum, J. A., Kurland, D. B., Gerzanich, V., & Simard, J. M. (2014) · Neurochemical Research · doi:10.1007/s11064-014-1374-3 · Cited by 158
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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