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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The glymphatic system is 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.
“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
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredAnimal studies have shown communication between the subarachnoid CSF space and perivascular compartments of the brain and spinal cord.
“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]
In 2012, a brain-wide pathway for convective transport of waste solutes from the brain was first described and denoted the glymphatic system.
“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]
Impaired glymphatic function has been suggested to be instrumental in a range of brain diseases, including Alzheimer's dementia, posttraumatic encephalopathy, ageing, sleep, depression, and exercise.
“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]
Animal studies report diverging findings regarding the sites of perivascular brain influx and efflux and direction of perivascular flow.
“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]
Increased width of perivascular spaces may be a determining factor for parenchymal tracer enrichment more than clearance.
“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]
Clearance of MRI contrast agents such as gadobutrol has previously been proposed to potentially resemble clearance of brain macromolecules with similar properties, including amyloidβ and tau.
“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]
Studies using injection of fluorescent tracers into the cisterna magna of mice have suggested that paravascular circulation occurs via cerebrospinal fluid convective flow through the extracellular spaces 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.
“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]
Curbing PCSK9 activity provides protection against the vascular aspects of Alzheimer's pathology.
“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]
The Results section on AQP4-dependent amyloid-β clearance reports reduced clearance in Aqp4-null mice, and the Discussion considers paravascular clearance in Alzheimer’s disease. Neither section addresses PCSK9 or whether curbing its activity protects against vascular pathology (searched: PCSK9 and its full name). (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe glymphatic system is a cerebrospinal fluid transport system that shares functions with peripheral lymphatic vessels, including export of excess interstitial fluid and proteins.
“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]
Glymphatic fluid transport is directionally polarized: influx along penetrating arteries, AQP4-supported entry into neuropil, and efflux along peri-venous spaces and cranial and spinal nerves.
“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]
Deletion of AQP4 reduces CSF tracer influx and solute efflux from the neuropil.
“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]
Polarized expression of AQP4 in astrocytic vascular endfeet facilitates glymphatic fluid transport and amyloid-β export in rodents.
“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]
Pulsatility of penetrating arteries supplements brain motion and drives CSF into the neuropil along periarterial spaces.
“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]
The expression of aquaporin-4 (AQP4) in astrocytes significantly influences the transport and clearance functions of the glymphatic system.
“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]
Neurotoxic molecules such as amyloid-β and tau are cleared from brain tissue along paravenous pathways (the glymphatic system).
“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]
Molecules from 0.8 to 70 kDa penetrate the glia limitans to varying degrees, whereas molecules from 150 to 2000 kDa are confined within the perivascular space.
“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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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× · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
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× · see citing works
“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× · see citing works
“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).”
BackgroundMathiisen, T. M., Lehre, K. P., Danbolt, N. C., & Ottersen, O. P. (2010) · Glia · doi:10.1002/glia.20990 · Cited by 917 · see citing works
Lehre, 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 890 · see citing works
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× · see citing works
“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× · see citing works
“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).”
BackgroundMethodInfluentialRennels, M. L., Gregory, T. F., Blaumanis, O. R., Fujimoto, K., & Grady, P. A. (1985) · Brain Research · doi:10.1016/0006-8993(85)91383-6 · Cited by 752 · cited 1× · see citing works
“(15, 28) in which horseradish peroxidase (molecular size, 40 kD) injected into subarachnoid space at the cisterna magna in the cat moved rapidly into the brain along para-arterial pathways.”
BackgroundWeller, R. O., Subash, M., Preston, S., Mazanti, I., & Carare, R. O. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00133.x · Cited by 682 · see citing works
NG2 cells generate both oligodendrocytes and gray matter astrocytes
Zhu, X., Bergles, D. E., & Nishiyama, A. (2007) · Development · doi:10.1242/dev.004895 · Cited by 678 · see citing works
Carare, R. O., Bernardes‐Silva, M., Newman, T. A., Page, A. M., Nicoll, J. A. R., Perry, V. H., & Weller, R. O. (2008) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00926.x · Cited by 665 · cited 1× · see citing works
“Our identification of paravenous pathways, particularly those surrounding the medial internal cerebral and caudal rhinal veins, as the primary route for clearance is in contrast to some studies identifying para-arterial sheaths as pathways for tracer clearance (26, 27).”
ResultMicrolymphatics and lymph flow
Schmid‐Schönbein, G. W. (1990) · Physiological Reviews · doi:10.1152/physrev.1990.70.4.987 · Cited by 615 · cited 1× · see citing works
“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).”
BackgroundJohnston, M., Zakharov, A., Papaiconomou, C., Salmasi, G., & Armstrong, D. (2004) · Cerebrospinal Fluid Research · doi:10.1186/1743-8454-1-2 · Cited by 572 · see citing works
Deane, R., Bell, R. D., Sagare, A. P., & Zloković, B. V. (2009) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152709787601867 · Cited by 549 · cited 1× · see citing works
“Soluble Aβ1–40 was cleared from the brain interstitium more rapidly than a comparably sized dextran molecule, suggesting that interaction between specific BBB Aβ efflux receptors with bulk flow–dependent clearance (46, 47) may occur.”
BackgroundSelf-citationAmiry-Moghaddam, M., Otsuka, T., Hurn, P. D., Traystman, R. J., Haug, F.-M., Froehner, S. C., Adams, M. E., Neely, J. D., Agre, P., Ottersen, O. P., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0437946100 · Cited by 534 · cited 1× · see citing works
“Mice with mislocalized or absent perivascular astrocytic AQP4, including a-syntrophin (35),mdx (36), and Aqp4 (37) knockout mice, show swollen endfeet and other pathological changes to perivascular astrocytes.”
BackgroundPhysiology of the choroid plexus.
Cserr, H. F. (1971) · Physiological Reviews · doi:10.1152/physrev.1971.51.2.273 · Cited by 514 · see citing works
Papadopoulos, M. C., & Verkman, A. S. (2007) · Pediatric Nephrology · doi:10.1007/s00467-006-0411-0 · Cited by 455 · cited 1× · see citing works
“AQP4 has been implicated in water uptake into the brain tissue during the evolution of cytotoxic edema, as well as in water clearance after vasogenic edema (30, 31).”
BackgroundCserr, H. F., Harling‐Berg, C. J., & Knopf, P. M. (1992) · Brain Pathology · doi:10.1111/j.1750-3639.1992.tb00703.x · Cited by 450 · see citing works
Reactive Astrocytes As Therapeutic Targets for CNS Disorders
Hamby, M. E., & Sofroniew, M. V. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.07.003 · Cited by 367 · see citing works
Drainage of interstitial fluid from different regions of rat brain
Szentistvanyi, I., Patlak, C. S., Ellis, R. A., & Cserr, H. F. (1984) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1984.246.6.f835 · Cited by 355 · see citing works
Haj‐Yasein, N. N., Vindedal, G. F., Eilert‐Olsen, M., Gundersen, G. A., Skare, Ø., Laake, P., Klungland, A., Thorén, A. E., Burkhardt, J. M., Ottersen, O. P., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1110655108 · Cited by 344 · see citing works
Self-citationEfflux of radiolabeled polyethylene glycols and albumin from rat brain
Cserr, H. F., Cooper, D. N., Suri, P. K., & Patlak, C. S. (1981) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1981.240.4.f319 · Cited by 323 · cited 6× · see citing works
“This suggested that their transit occurs via bulk CSF flow through the paravascular spaces (4, 16).”
BackgroundInfluentialHadaczek, P., Yamashita, Y., Mirek, H., Tamas, L. B., Bohn, M. C., Noble, C. O., Park, J. W., & Bankiewicz, K. S. (2006) · Molecular Therapy · doi:10.1016/j.ymthe.2006.02.018 · Cited by 312 · see citing works
Koh, L., Zakharov, A., & Johnston, M. G. (2005) · Cerebrospinal Fluid Research · doi:10.1186/1743-8454-2-6 · Cited by 298 · cited 2× · see citing works
“The relationship between the CSF compartment and the peripheral lymphatics is well established (8).”
BackgroundMechanisms to explain the reverse perivascular transport of solutes out of the brain
Schley, D., Carare-Nnadi, R., Please, C. P., Perry, V. H., & Weller, R. O. (2006) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2005.07.005 · Cited by 293 · see citing works
Dorr, A. E., Sled, J. G., & Kabani, N. J. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2006.12.040 · Cited by 266 · see citing works
Zlokovic, B. V., Deane, R., Sagare, A. P., Bell, R. D., & Winkler, E. A. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07002.x · Cited by 261 · see citing works
Self-citationThrane, A. S., Rappold, P. M., Fujita, T., Torres, A., Bekar, L. K., Takano, T., Peng, W., Wang, F., Rangroo Thrane, V., Enger, R., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015217108 · Cited by 254 · see citing works
Self-citationDistribution of extracellular tracers in perivascular spaces of the rat brain
Ichimura, T., Fraser, P. A., & Cserr, H. F. (1991) · Brain Research · doi:10.1016/0006-8993(91)91275-6 · Cited by 215 · cited 5× · see citing works
“These findings were rebutted by Cserr and colleagues, who concluded that paravascular influx of subarachnoid CSF was “slow and variable in direction” (11, 29).”
BackgroundMethodInfluentialBradbury, M. W. B., & Westrop, R. J. (1983) · The Journal of Physiology · doi:10.1113/jphysiol.1983.sp014731 · Cited by 211 · see citing works
Rapid solute transport throughout the brain via paravascular fluid pathways.
Rennels, M. L., Blaumanis, O. R., & Grady, P. A. (1990) · PubMed · Cited by 204 · see citing works
Aquaporin‐4 deficiency in skeletal muscle and brain of dystrophic mdx mice
Frigeri, A., Nicchia, G. P., Nico, B., Quondamatteo, F., Herken, R., Roncali, L., & Svelto, M. (2001) · The FASEB Journal · doi:10.1096/fj.00-0260com · Cited by 197 · cited 1× · see citing works
“Mice with mislocalized or absent perivascular astrocytic AQP4, including α-syntrophin (35), mdx (36), and Aqp4 (37) knockout mice, show swollen endfeet and other pathological changes to perivascular astrocytes.”
BackgroundProinflammatory role of aquaporin‐4 in autoimmune neuroinflammation
Li, L., Zhang, H., Varrin‐Doyer, M., Zamvil, S. S., & Verkman, A. S. (2011) · The FASEB Journal · doi:10.1096/fj.10-177279 · Cited by 190 · cited 1× · see citing works
“Indeed, Aqp4-null mice exhibit reduced neuroinflammation after intracerebral lipopolysaccharide injection (50).”
BackgroundMicroscopic morphology and histology of the human meninges
Weller, R. O. (2005) · Morphologie · doi:10.1016/s1286-0115(05)83235-7 · Cited by 176 · cited 6× · see citing works
“Carare RO, Bernardes-Silva M, Newman TA, Page AM, Nicoll JA, Perry VH, Weller RO.”
BackgroundResultInfluentialThe absorption of cerebrospinal fluid into the venous system
Weed, L. H. (1923) · American Journal of Anatomy · doi:10.1002/aja.1000310302 · Cited by 166 · cited 1× · see citing works
“These recognized patterns of drainage initially led to the concept that CSF serves a “lymphatic” function through its exchange with brain ISF along paravascular spaces (6, 25).”
BackgroundProescholdt, M. G., Hutto, B., Brady, L. S., & Herkenham, M. A. (1999) · Neuroscience · doi:10.1016/s0306-4522(99)00417-0 · Cited by 165 · cited 2× · see citing works
“Previous studies that have evaluated the penetration of subarachnoid CSF into the brain have used tracers such as inulin (molecular size, ~5 kD), albumin (molecular size, 66 kD), and dextrans (molecular size, 3 to 2000 kD) (10, 11).”
MethodPerivascular instruction of cell genesis and fate in the adult brain
Goldman, S. A., & Chen, Z. (2011) · Nature Neuroscience · doi:10.1038/nn.2963 · Cited by 153 · cited 1× · see citing works
“Additionally, paravascular routes may be conduits for cell migration, molecularly distinct and functionally overlapping with the perivascular niches for cell genesis and migration in the adult brain parenchyma (52).”
BackgroundSelf-citationThe concentration of glial fibrillary acidic protein increases with age in the mouse and rat brain
O'Callaghan, J. P., & Miller, D. B. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90057-q · Cited by 152 · see citing works
Aquaporin-4-Deficient Mice Have Increased Extracellular Space without Tortuosity Change
Yao, X., Hrabětová, S., Nicholson, C., & Manley, G. T. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0257-08.2008 · Cited by 147 · see citing works
Altered blood–brain barrier integrity in adult aquaporin-4 knockout mice
Zhou, J., Kong, H., Hua, X., Xiao, M., Ding, J., & Hu, G. (2008) · Neuroreport · doi:10.1097/wnr.0b013e3282f2b4eb · Cited by 144 · cited 1× · see citing works
“Mice with mislocalized or absent perivascular astrocytic AQP4, including α-syntrophin (35), mdx (36), and Aqp4 (37) knockout mice, show swollen endfeet and other pathological changes to perivascular astrocytes.”
BackgroundThe Choroid Plexus Removes β-Amyloid from Brain Cerebrospinal Fluid
Crossgrove, J. S., Li, G. J., & Zheng, W. (2005) · Experimental Biology and Medicine · doi:10.1177/153537020523001011 · Cited by 130 · cited 1× · see citing works
“Scienc Soluble Ab is also present in the CSF, from which it may be cleared by transport across the choroid plexus (20), as well as by bulk CSF turnover (21).”
BackgroundAQP4 gene deletion in mice does not alter blood–brain barrier integrity or brain morphology
Saadoun, S., Tait, M. J., Reza, A., Davies, D. C., Bell, B. A., Verkman, A. S., & Papadopoulos, M. C. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.03.069 · Cited by 121 · see citing works
Boulton, M., Yonung, A., Hay, J. B., Armstrong, D. W., Flessner, M. F., Schwartz, M. L., & Johnston, M. (1996) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1996.tb01111.x · Cited by 120 · see citing works
Sérot, J., Zmudka, J., & Jouanny, P. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-111964 · Cited by 114 · see citing works
Water and solute secretion by the choroid plexus
Prætorius, J. (2006) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-006-0170-6 · Cited by 106 · cited 1× · see citing works
“CSF formed in the choroid plexi flows through the cerebral ventricles and the subarachnoid space to its ultimate sites of reabsorption into the bloodstream via arachnoid villi of the dural sinuses, along cranial nerve sheaths or through the nasal lymphatics (3, 7, 8).”
BackgroundGroothuis, D. R., Vavra, M. W., Schlageter, K. E., Kang, E. W.-Y., Itskovich, A. C., Hertzler, S., Allen, C. V., & Lipton, H. L. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600315 · Cited by 95 · cited 3× · see citing works
“One of the hallmarks of bulk flow, compared to simple diffusion, is the independence of solute movement from molecular size (4, 46), because all solutes are carried along with the moving medium at the same rate of fluid flow.”
BackgroundBall, K. K., Cruz, N. F., Mrak, R. E., & Dienel, G. A. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.206 · Cited by 93 · see citing works
Recent advances in (patho)physiology of astroglia
Verkhratsky, A., & Parpura, V. (2010) · Acta Pharmacologica Sinica · doi:10.1038/aps.2010.108 · Cited by 82 · see citing works
Clearance of Amyloid-β Peptide Across the Choroid Plexus in Alzheimers Disease
Alvira, X., & Carro, E. (2010) · Current Aging Science · doi:10.2174/1874609811003030219 · Cited by 78 · see citing works
Bulk flow of cerebrospinal fluid into brain in response to acute hyperosmolality
Pullen, R. G. L., Depasquale, M. J., & Cserr, H. F. (1987) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1987.253.3.f538 · Cited by 75 · see citing works
Some Problems of the Origin, Circulation and Absorption of the Cerebrospinal Fluid
Flexner, L. B. (1933) · The Quarterly Review of Biology · doi:10.1086/394447 · Cited by 62 · cited 2× · see citing works
“The cerebrospinal fluid (CSF) of the central nervous system (CNS) has been thought to play a role in solute clearance from the brain (6).”
BackgroundEilert‐Olsen, M., Haj‐Yasein, N. N., Vindedal, G. F., Enger, R., Gundersen, G. A., Hoddevik, E. H., Petersen, P. H., Haug, F. Š., Skare, Ø., Adams, M. E., et al. (2011) · Glia · doi:10.1002/glia.22277 · Cited by 52 · see citing works
Self-citationQuantification of regional glial fibrillary acidic protein levels in Alzheimer's disease
Ross, G. W., O'Callaghan, J. P., Sharp, D. S., Petrovitch, H., Miller, D. B., Abbott, R. D., Nelson, J., Launer, L. J., Foley, D., Burchfiel, C. M., et al. (2003) · Acta Neurologica Scandinavica · doi:10.1034/j.1600-0404.2003.02098.x · Cited by 42 · see citing works
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Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226 · see citing works
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 · see citing works
Self-citationAlzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · see citing works
Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076 · see citing works
The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease
Iadecola, C. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.030 · Cited by 2,480 · see citing works
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,294 · see citing works
A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules
Aspelund, A., Antila, S., Proulx, S. T., Karlsen, T. V., Karaman, S., Detmar, M., Wiig, H., & Alitalo, K. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20142290 · Cited by 2,198 · see citing works
The spectrum of disease in chronic traumatic encephalopathy
McKee, A. C., Stein, T. D., Nowinski, C. J., Stern, R. A., Daneshvar, D. H., Alvarez, V. E., Lee, H.-S., Hall, G., Wojtowicz, S. M., Baugh, C. M., et al. (2013) · Brain · doi:10.1093/brain/aws307 · Cited by 2,098 · see citing works
The glymphatic system: a beginner's guide
Jessen, N. A., Munk, A. S. F., Lundgaard, I., & Nedergaard, M. (2015) · Neurochemical Research · doi:10.1007/s11064-015-1581-6 · Cited by 2,075 · see citing works
Self-citationA molecular atlas of cell types and zonation in the brain vasculature
Vanlandewijck, M., He, L., Mäe, M. A., Andrae, J., Ando, K., Del Gaudio, F., Nahar, K., Lebouvier, T., Laviña, B., Gouveia, L., et al. (2018) · Nature · doi:10.1038/nature25739 · Cited by 2,074 · see citing works
Clearance systems in the brain—implications for Alzheimer disease
Tarasoff-Conway, J. M., Carare, R. O., Osorio, R. S., Glodzik, L., Butler, T., Fieremans, E., Axel, L., Rusinek, H., Nicholson, C., Zlokovic, B. V., et al. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.119 · Cited by 1,678 · see citing works
Verkhratsky, A., & Nedergaard, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00042.2016 · Cited by 1,678 · see citing works
Self-citationThe glymphatic pathway in neurological disorders.
Rasmussen, M. K., Mestre, H., & Nedergaard, M. (2018) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30318-1 · Cited by 1,560 · see citing works
Self-citationImpairment of paravascular clearance pathways in the aging brain
Kress, B. T., Iliff, J. J., Xia, M., Wang, M., Wei, H. S., Zeppenfeld, D., Xie, L., Kang, H., Xu, Q., Liew, J. A., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24271 · Cited by 1,521 · see citing works
“nel and measuring the thresholded area as a percentage of the overall region area, as described previously.(4) The fluorescence area”
BackgroundMethodInfluentialSelf-citationFunctional aspects of meningeal lymphatics in ageing and Alzheimer’s disease
Da Mesquita, S., Louveau, A., Vaccari, A., Smirnov, I., Cornelison, R. C., Kingsmore, K. M., Contarino, C., Onengut-Gumuscu, S., Farber, E., Raper, D., et al. (2018) · Nature · doi:10.1038/s41586-018-0368-8 · Cited by 1,445 · see citing works
Cerebral Arterial Pulsation Drives Paravascular CSF–Interstitial Fluid Exchange in the Murine Brain
Iliff, J. J., Wang, M., Zeppenfeld, D. M., Venkataraman, A., Plog, B. A., Liao, Y., Deane, R., & Nedergaard, M. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1592-13.2013 · Cited by 1,319 · see citing works
Self-citationA Cellular Perspective on Brain Energy Metabolism and Functional Imaging
Magistretti, P. J., & Allaman, I. (2015) · Neuron · doi:10.1016/j.neuron.2015.03.035 · Cited by 1,285 · see citing works
The far-reaching scope of neuroinflammation after traumatic brain injury
Simon, D. W., McGeachy, M. J., Bayır, H., Clark, R. S. B., Loane, D. J., & Kochanek, P. M. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.13 · Cited by 1,190 · see citing works
From blood–brain barrier to blood–brain interface: new opportunities for CNS drug delivery
Banks, W. A. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.21 · Cited by 1,204 · see citing works
Brain-wide pathway for waste clearance captured by contrast-enhanced MRI
Iliff, J. J., Lee, H., Yu, M., Feng, T., Logan, J., Nedergaard, M., & Benveniste, H. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67677 · Cited by 1,148 · see citing works
Self-citationTaoka, T., Masutani, Y., Kawai, H., Nakane, T., Matsuoka, K., Yasuno, F., Kishimoto, T., & Naganawa, S. (2017) · Japanese Journal of Radiology · doi:10.1007/s11604-017-0617-z · Cited by 1,194 · see citing works
Impairment of Glymphatic Pathway Function Promotes Tau Pathology after Traumatic Brain Injury
Iliff, J. J., Chen, M. J., Plog, B. A., Zeppenfeld, D. M., Soltero, M., Yang, L., Singh, I., Deane, R., & Nedergaard, M. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3020-14.2014 · Cited by 1,159 · see citing works
Self-citationFlow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension.
Mestre, H., Tithof, J., Du, T., Song, W., Peng, W., Sweeney, A. M., Olveda, G., Thomas, J. H., Nedergaard, M., & Kelley, D. H. (2018) · Nature Communications · doi:10.1038/s41467-018-07318-3 · Cited by 1,110 · see citing works
Self-citationGlymphatic failure as a final common pathway to dementia
Nedergaard, M., & Goldman, S. A. (2020) · Science · doi:10.1126/science.abb8739 · Cited by 1,145 · see citing works
Self-citationPericytes of the neurovascular unit: key functions and signaling pathways
Sweeney, M. D., Ayyadurai, S., & Zlokovic, B. V. (2016) · Nature Neuroscience · doi:10.1038/nn.4288 · Cited by 1,125 · see citing works
Generation of circadian rhythms in the suprachiasmatic nucleus
Hastings, M. H., Maywood, E. S., & Brancaccio, M. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0026-z · Cited by 1,065 · see citing works
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994 · see citing works
“Abbreviations AD: Alzheimer’s disease; APOE: Apolipoprotein E; Aβ: β-Amyloid; APP: Amyloid precursor protein; KCC2: K-Cl cotransporter 2; GABA : γaminobutyric acid; sAPP: Soluble amyloid precursor proteins; CNS: Central nervous system; PS1/2: Presenilins 1/2; CSF: Cerebral spinal fluid; LRP1: Lowdensity lipoprotein re…”
BackgroundInfluentialGlutamate as a neurotransmitter in the healthy brain
Zhou, Y., & Danbolt, N. C. (2014) · Journal of Neural Transmission · doi:10.1007/s00702-014-1180-8 · Cited by 989 · see citing works
Astrocyte Crosstalk in CNS Inflammation
Linnerbauer, M., Wheeler, M. A., & Quintana, F. J. (2020) · Neuron · doi:10.1016/j.neuron.2020.08.012 · Cited by 989 · see citing works
“Moreover the anatomical location of astrocyte endfeet enables them to react to soluble factors in the meningeal space (Iliff et al., 2012; Sofroniew, 2015b).”
BackgroundCNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature.
Louveau, A., Herz, J., Alme, M. N., Salvador, A. F., Dong, M. Q., Viar, K. E., Herod, S. G., Knopp, J., Setliff, J. C., Lupi, A. L., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0227-9 · Cited by 956 · see citing works
Cerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways
Greenberg, S. M., Bacskai, B. J., Hernandez-Guillamon, M., Pruzin, J., Sperling, R., & van Veluw, S. J. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-019-0281-2 · Cited by 947 · see citing works
Blood-brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound
Lipsman, N., Meng, Y., Bethune, A. J., Huang, Y., Lam, B., Masellis, M., Herrmann, N., Heyn, C., Aubert, I., Boutet, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04529-6 · Cited by 950 · see citing works
Perivascular spaces in the brain: anatomy, physiology and pathology
Wardlaw, J. M., Benveniste, H., Nedergaard, M., Zlokovic, B. V., Mestre, H., Lee, H., Doubal, F. N., Brown, R., Ramirez, J., MacIntosh, B. J., et al. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0312-z · Cited by 870 · see citing works
Self-citationMechanisms linking circadian clocks, sleep, and neurodegeneration
Musiek, E. S., & Holtzman, D. M. (2016) · Science · doi:10.1126/science.aah4968 · Cited by 878 · see citing works
β-Amyloid accumulation in the human brain after one night of sleep deprivation
Shokri-Kojori, E., Wang, G.-J., Wiers, C. E., Demiral, S. B., Guo, M., Kim, S. W., Lindgren, E., Ramirez, V., Zehra, A., Freeman, C., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1721694115 · Cited by 893 · see citing works
Self-citationThe movers and shapers in immune privilege of the CNS
Engelhardt, B., Vajkoczy, P., & Weller, R. O. (2017) · Nature Immunology · doi:10.1038/ni.3666 · Cited by 893 · see citing works
A human brain vascular atlas reveals diverse mediators of Alzheimer’s risk
Yang, A. C., Vest, R. T., Kern, F., Lee, D. P., Agam, M., Maat, C. A., Losada, P. M., Chen, M. B., Schaum, N., Khoury, N., et al. (2022) · Nature · doi:10.1038/s41586-021-04369-3 · Cited by 797 · see citing works
A neurocentric perspective on glioma invasion
Cuddapah, V. A., Robel, S., Watkins, S., & Sontheimer, H. W. (2014) · Nature reviews. Neuroscience · doi:10.1038/nrn3765 · Cited by 826 · see citing works
A new look at cerebrospinal fluid circulation
Brinker, T., Stopa, E., Morrison, J., & Klinge, P. (2014) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-11-10 · Cited by 819 · see citing works
Multi-sensory Gamma Stimulation Ameliorates Alzheimer’s-Associated Pathology and Improves Cognition
Martorell, A. J., Paulson, A. L., Suk, H.-J., Abdurrob, F., Drummond, G. T., Guan, W., Young, J. Z., Kim, D. N.-W., Kritskiy, O., Barker, S. J., et al. (2019) · Cell · doi:10.1016/j.cell.2019.02.014 · Cited by 798 · see citing works
The Glymphatic System in Central Nervous System Health and Disease: Past, Present, and Future
Plog, B. A., & Nedergaard, M. (2017) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-051217-111018 · Cited by 780 · see citing works
Self-citationThe blood-brain barrier in Alzheimer’s disease
Zenaro, E., Piacentino, G., & Constantin, G. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.07.007 · Cited by 767 · see citing works
Aquaporin-4-dependent glymphatic solute transport in the rodent brain
Mestre, H., Hablitz, L. M., Xavier, A. L., Feng, W., Zou, W., Pu, T., Monai, H., Murlidharan, G., Castellanos Rivera, R. M., Simon, M. J., et al. (2018) · eLife · doi:10.7554/elife.40070 · Cited by 738 · see citing works
Self-citationThe blood–brain barrier in health and disease: Important unanswered questions
Profaci, C. P., Munji, R. N., Pulido, R. S., & Daneman, R. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20190062 · Cited by 777 · see citing works
“P-selectin and E-selectin mediate the rolling of leukocytes along the endothelium, ICAM1 and VCAM1 mediate firm adhesion, and proteins like PLVAP—also up-regulated in disease—aid in transmigration across ECs (Engelhardt and Ransohoff, 2012; Ioannidou et al., 2006).”
BackgroundPhysiological Roles of Aquaporin-4 in Brain
Nagelhus, E. A., & Ottersen, O. P. (2013) · Physiological Reviews · doi:10.1152/physrev.00011.2013 · Cited by 766 · see citing works
Self-citationAstrocyte roles in traumatic brain injury
Burda, J. E., Bernstein, A. M., & Sofroniew, M. V. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.03.020 · Cited by 758 · see citing works
Iadecola, C., Yaffe, K., Biller, J., Bratzke, L. C., Faraci, F. M., Gorelick, P. B., Gulati, M., Kamel, H., Knopman, D. S., Launer, L. J., et al. (2016) · Hypertension · doi:10.1161/hyp.0000000000000053 · Cited by 746 · see citing works
Aquaporin water channels in the nervous system
Papadopoulos, M. C., & Verkman, A. S. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3468 · Cited by 748 · see citing works
Glymphatic MRI in idiopathic normal pressure hydrocephalus
Ringstad, G., Vatnehol, S. A. S., & Eide, P. K. (2017) · Brain · doi:10.1093/brain/awx191 · Cited by 722 · see citing works
Brain immunology and immunotherapy in brain tumours
Sampson, J. H., Gunn, M. D., Fecci, P. E., & Ashley, D. M. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0224-7 · Cited by 733 · see citing works
History and progress of hypotheses and clinical trials for Alzheimer’s disease
Liu, P.-P., Xie, Y., Meng, X.-Y., & Kang, J.-S. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0063-8 · Cited by 723 · see citing works
Circadian control of brain glymphatic and lymphatic fluid flow
Hablitz, L. M., Plá, V., Giannetto, M., Vinitsky, H. S., Stæger, F. F., Metcalfe, T., Nguyen, R., Benrais, A., & Nedergaard, M. (2020) · Nature Communications · doi:10.1038/s41467-020-18115-2 · Cited by 704 · see citing works
Self-citationMechanisms of macular edema: Beyond the surface
Daruich, A., Matet, A., Moulin, A., Kowalczuk, L., Nicolas, M., Sellam, A., Rothschild, P.-R., Omri, S., Gélizé, E., Jonet, L., et al. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.10.006 · Cited by 733 · see citing works
Functional characterization of the dural sinuses as a neuroimmune interface
Rustenhoven, J., Drieu, A., Mamuladze, T., de Lima, K. A., Dykstra, T., Wall, M., Papadopoulos, Z., Kanamori, M., Salvador, A. F., Baker, W., et al. (2021) · Cell · doi:10.1016/j.cell.2020.12.040 · Cited by 685 · see citing works
Nedergaard, M. (2013) · Science · doi:10.1126/science.1240514 · Cited by 704 · see citing works
Self-citationAlzheimer’s disease: A matter of blood–brain barrier dysfunction?
Montagne, A., Zhao, Z., & Zlokovic, B. V. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20171406 · Cited by 672 · see citing works
Development and functions of the choroid plexus–cerebrospinal fluid system
Lun, M. P., Monuki, E. S., & Lehtinen, M. K. (2015) · Nature reviews. Neuroscience · doi:10.1038/nrn3921 · Cited by 682 · see citing works
Ma, Q., Ineichen, B. V., Detmar, M., & Proulx, S. T. (2017) · Nature Communications · doi:10.1038/s41467-017-01484-6 · Cited by 690 · see citing works
Revisiting the Mechanisms of CNS Immune Privilege
Louveau, A., Harris, T. H., & Kipnis, J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.006 · Cited by 682 · see citing works
Benedet, A. L., Milà-Alomà, M., Vrillon, A., Ashton, N. J., Pascoal, T. A., Lussier, F., Karikari, T. K., Hourregue, C., Cognat, E., Dumurgier, J., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2021.3671 · Cited by 638 · see citing works
Zeppenfeld, D. M., Simon, M., Haswell, J. D., D’Abreo, D., Murchison, C., Quinn, J. F., Grafe, M. R., Woltjer, R. L., Kaye, J., & Iliff, J. J. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2016.4370 · Cited by 651 · see citing works
Self-citationAbsinta, M., Ha, S.-K., Nair, G., Sati, P., Luciano, N. J., Palisoc, M., Louveau, A., Zaghloul, K. A., Pittaluga, S., Kipnis, J., et al. (2017) · eLife · doi:10.7554/elife.29738 · Cited by 643 · see citing works
Impaired glymphatic function and clearance of tau in an Alzheimer’s disease model
Harrison, I. F., Ismail, O., Machhada, A., Colgan, N. C., Ohene, Y., Nahavandi, P., Ahmed, Z., Fisher, A., Meftah, S., Murray, T. K., et al. (2020) · Brain · doi:10.1093/brain/awaa179 · Cited by 663 · see citing works
Self-citationFrom Sewer to Saviour—Targeting the Lymphatic System to Promote Drug Exposure and Activity
Trevaskis, N. L., Kaminskas, L. M., & Porter, C. J. H. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4608 · Cited by 654 · see citing works
Hablitz, L. M., Vinitsky, H. S., Sun, Q., Stæger, F. F., Sigurdsson, B., Mortensen, K. N., Lilius, T. O., & Nedergaard, M. (2019) · Science Advances · doi:10.1126/sciadv.aav5447 · Cited by 629 · see citing works
Self-citationUnderstanding the functions and relationships of the glymphatic system and meningeal lymphatics
Louveau, A., Plog, B. A., Antila, S., Alitalo, K., Nedergaard, M., & Kipnis, J. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90603 · Cited by 640 · see citing works
Self-citation3D bioprinting of tissues and organs for regenerative medicine
Vijayavenkataraman, S., Yan, W.-C., Lu, W. F., Wang, C., & Fuh, J. Y. H. (2018) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2018.07.004 · Cited by 634 · see citing works
The Brain’s Glymphatic System: Current Controversies
Mestre, H., Mori, Y., & Nedergaard, M. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.04.003 · Cited by 609 · see citing works
Self-citationMechanisms of fluid movement into, through and out of the brain: evaluation of the evidence
Hladky, S. B., & Barrand, M. A. (2014) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-11-26 · Cited by 633 · see citing works
Rasmussen, M. K., Mestre, H., & Nedergaard, M. (2021) · Physiological Reviews · doi:10.1152/physrev.00031.2020 · Cited by 622 · see citing works
Self-citationApoE and Aβ in Alzheimer’s Disease: Accidental Encounters or Partners?
Kanekiyo, T., Xu, H., & Bu, G. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.045 · Cited by 608 · see citing works
Suppression of glymphatic fluid transport in a mouse model of Alzheimer's disease
Peng, W., Achariyar, T. M., Li, B., Liao, Y., Mestre, H., Hitomi, E., Regan, S., Kasper, T., Peng, S., Ding, F., et al. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.05.015 · Cited by 580 · see citing works
Self-citationMolecular pathophysiology of cerebral edema
Stokum, J. A., Gerzanich, V., & Simard, J. M. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x15617172 · Cited by 596 · see citing works
The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system?
Abbott, N. J., Pizzo, M. E., Preston, J. E., Janigro, D., & Thorne, R. G. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1812-4 · Cited by 593 · see citing works
Interaction of Microglia and Astrocytes in the Neurovascular Unit
Liu, L., Liu, J., Bao, J.-S., Bai, Q.-Q., & Wang, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01024 · Cited by 591 · see citing works
Aquaporins: important but elusive drug targets
Verkman, A. S., Anderson, M. O., & Papadopoulos, M. C. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4226 · Cited by 589 · see citing works
The Neuropathology of Chronic Traumatic Encephalopathy
McKee, A. C., Stein, T. D., Kiernan, P. T., & Alvarez, V. E. (2015) · Brain Pathology · doi:10.1111/bpa.12248 · Cited by 585 · see citing works
Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease
Erickson, M. A., & Banks, W. A. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.135 · Cited by 572 · see citing works
Verghese, P. B., Castellano, J. M., Garai, K., Wang, Y., Jiang, H., Shah, A., Bu, G., Frieden, C., & Holtzman, D. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1220484110 · Cited by 556 · see citing works
Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature
Ayata, C., & Lauritzen, M. (2015) · Physiological Reviews · doi:10.1152/physrev.00027.2014 · Cited by 555 · see citing works
Disruption of astrocyte–vascular coupling and the blood–brain barrier by invading glioma cells
Watkins, S., Robel, S., Kimbrough, I. F., Robert, S. M., Ellis‐Davies, G. C. R., & Sontheimer, H. W. (2014) · Nature Communications · doi:10.1038/ncomms5196 · Cited by 551 · see citing works
Brain-wide glymphatic enhancement and clearance in humans assessed with MRI.
Ringstad, G., Valnes, L. M., Dale, A. M., Pripp, A. H., Vatnehol, S.-A. S., Emblem, K. E., Mardal, K.-A., & Eide, P. K. (2018) · JCI Insight · doi:10.1172/jci.insight.121537 · Cited by 533 · see citing works
“Moreover, animal studies report diverging findings regarding the sites of perivascular brain influx and efflux and direction of perivascular flow (7, 15, 16).”
InfluentialAstrocytes in chronic pain and itch
Ji, R., Donnelly, C. R., & Nedergaard, M. (2019) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0218-1 · Cited by 553 · see citing works
Self-citationSleep physiology, pathophysiology, and sleep hygiene
Baranwal, N., Yu, P. K., & Siegel, N. S. (2023) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2023.02.005 · Cited by 540 · see citing works
Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system.
Plog, B. A., Dashnaw, M. L., Hitomi, E., Peng, W., Liao, Y., Lou, N., Deane, R., & Nedergaard, M. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.3742-14.2015 · Cited by 525 · see citing works
Self-citationThe Glymphatic System and Waste Clearance with Brain Aging: A Review
Benveniste, H., Liu, X., Koundal, S., Sanggaard, S., Lee, H., & Wardlaw, J. (2019) · Gerontology · doi:10.1159/000490349 · Cited by 517 · see citing works
Self-citationDeletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits
Xu, Z., Xiao, N., Chen, Y., Huang, H., Marshall, C., Gao, J., Cai, Z., Wu, T., Hu, G., & Xiao, M. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0056-1 · Cited by 500 · see citing works
Cerebrospinal fluid influx drives acute ischemic tissue swelling
Mestre, H., Du, T., Sweeney, A. M., Liu, G., Samson, A. J., Peng, W., Mortensen, K. N., Stæger, F. F., Bork, P. A. R., Bashford, L., et al. (2020) · Science · doi:10.1126/science.aax7171 · Cited by 494 · see citing works
Self-citationCSF, blood-brain barrier, and brain drug delivery
Pardridge, W. M. (2016) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.2016.1171315 · Cited by 508 · see citing works
Physiological blood–brain transport is impaired with age by a shift in transcytosis
Yang, A. C., Stevens, M. Y., Chen, M. B., Lee, D. P., Stähli, D., Gate, D., Contrepois, K., Chen, W., Iram, T., Zhang, L., et al. (2020) · Nature · doi:10.1038/s41586-020-2453-z · Cited by 477 · see citing works
Glymphatic clearance function in patients with cerebral small vessel disease
Zhang, W., Zhou, Y., Wang, J., Gong, X., Chen, Z., Zhang, X., Cai, J., Chen, S., Fang, L., Sun, J., et al. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118257 · Cited by 493 · see citing works
The Meningeal Lymphatic System: A New Player in Neurophysiology
Da Mesquita, S., Fu, Z., & Kipnis, J. (2018) · Neuron · doi:10.1016/j.neuron.2018.09.022 · Cited by 479 · see citing works
Development and plasticity of meningeal lymphatic vessels
Antila, S., Karaman, S., Nurmi, H. J., Airavaara, M., Voutilainen, M. H., Mathivet, T., Chilov, D., Li, Z., Koppinen, T. K., Park, J., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20170391 · Cited by 469 · see citing works
Biological functions of lymphatic vessels
Petrova, T. V., & Koh, G. Y. (2020) · Science · doi:10.1126/science.aax4063 · Cited by 461 · see citing works
The Glymphatic System: A Novel Component of Fundamental Neurobiology
Hablitz, L. M., & Nedergaard, M. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.0619-21.2021 · Cited by 480 · see citing works
“The features unique to discovery of the glymphatic system were as follows: (1) the direction of fluid transport, starting with entry of CSF at the periarterial space followed by exit of “dirty” interstitial fluid along the perivenous spaces; (2) a metabolic waste product, amyloid-b , was shown to be exported via the g…”
BackgroundInfluentialSelf-citationImmunoneuropsychiatry — novel perspectives on brain disorders
Pape, K., Tamouza, R., Leboyer, M., & Zipp, F. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0174-4 · Cited by 455 · see citing works
Boire, A. A., Brastianos, P. K., Garzia, L., & Valiente, M. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0220-y · Cited by 455 · see citing works
A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans
Spector, R., Snodgrass, S. R., & Johanson, C. E. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.07.027 · Cited by 445 · see citing works
The Effect of Body Posture on Brain Glymphatic Transport
Lee, H. J., Xie, L., Yu, M., Kang, H., Feng, T., Deane, R., Logan, J., Nedergaard, M., & Benveniste, H. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.1625-15.2015 · Cited by 447 · see citing works
Self-citationIntegrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis
Schafflick, D., Xu, C. A., Hartlehnert, M., Cole, M. B., Schulte‐Mecklenbeck, A., Lautwein, T., Wolbert, J., Heming, M., Meuth, S. G., Kuhlmann, T., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14118-w · Cited by 441 · see citing works
“Exclusion criteria for all patients were: (1) immunologically relevant comorbidities (e.”
BackgroundMethodInfluential
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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