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
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“1 nm, respectively (9)] pass the endfeet in a size- and structure-dependent manner (Fig.”
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“Both lymphocytes and antigen-presenting cells in the subarachnoid CSF (49) may detect interstitial antigens delivered to the CSF by paravenous bulk outflow.”
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“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).”
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“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
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“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).”
BackgroundMethodInfluential
Cited by
Sorted by citations
Items 701–800 of 1,031
Cerebral small vessel disease: A glymphopathy?
Benveniste, H., & Nedergaard, M. (2021) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2021.07.006 · Cited by 94
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“As an example, Müller cells and astrocytes express the water channel aquaporin-4 (AQP4) in a distribution enriched at the endfeet bordering the vitreous and retinal vessels.”
BackgroundInfluentialGullotta, G. S., Costantino, G., Sortino, M. A., & Spampinato, S. F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119144 · Cited by 97
Glymphatic System Impairment Contributes to the Formation of Brain Edema After Ischemic Stroke
Zhu, J., Mo, J., Liu, K., Chen, Q., Li, Z., He, Y., Chang, Y., Lin, C., Yu, M., Xu, Y., et al. (2024) · Stroke · doi:10.1161/strokeaha.123.045941 · Cited by 94
“14 Anatomically, GS is made up of 3 key parts: para-arterial influx of CSF into the brain parenchyma, convective fluid flow facilitated by high-polarized AQP4 (aquaporin-4) water channels, and para-venous or para-nerve efflux of ISF into the meninges and deep cervical lymph nodes (dCLNs).”
BackgroundCilia in the choroid plexus: their roles in hydrocephalus and beyond
Narita, K., & Takeda, S. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00039 · Cited by 94
Liquid biopsies in patients with diffuse glioma
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Cerebrospinal fluid and the early brain development of autism
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Temozolomide treatment outcomes and immunotherapy efficacy in brain tumor
Hotchkiss, K. M., & Sampson, J. H. (2020) · Journal of Neuro-Oncology · doi:10.1007/s11060-020-03598-2 · Cited by 93
The role of brain perivascular space burden in early-stage Parkinson’s disease
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Molecular mechanisms governing aquaporin relocalisation
Markou, A., Unger, L., Abir-Awan, M., Saadallah, A., Halsey, A. M., Balklava, Z., Conner, M. T., Törnroth‐Horsefield, S., Greenhill, S., Conner, A. C., et al. (2021) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2021.183853 · Cited by 91
Sun, C., Lin, L., Yin, L., Hao, X., Tian, J., Zhang, X., Ren, Y., Li, C., & Yang, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.870029 · Cited by 91
“Besides, loss of AQP4 polarization impairs the glymphatic system, a newlydiscovered waste clearance system in the brain (17), causing toxic protein deposition and cognitive deficits (18, 19).”
BackgroundMoreira, R., Nóbrega, C., de Almeida, L. P., & Mendonça, L. S. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02511-7 · Cited by 98
Wood, K. H., Nenert, R. E., Miften, A. M., Kent, G. W., Sleyster, M., Memon, R. A., Joop, A., Pilkington, J., Memon, A., Wilson, R. N., et al. (2024) · Movement Disorders · doi:10.1002/mds.29908 · Cited by 92
Redefining CNS immune privilege
Smyth, L. C. D., & Kipnis, J. (2025) · Nature Reviews Immunology · doi:10.1038/s41577-025-01175-0 · Cited by 80
“There has been a revival of interest in CSF due to the conception of the glymphatic hypothesis 29 , a framework describing the exchange between CSF and CNS interstitial fluid that enables the removal of wastes from the CNS 29 .”
InfluentialIntegrating the Glioblastoma Microenvironment Into Engineered Experimental Models
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AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis
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Multifaceted roles of pericytes in central nervous system homeostasis and disease
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“Also, the pericyte loss may interfere with the glymphatic system and thereby exacerbate neuronal toxicity.(122) Another rodent model of vascular dementia generated from administration of cholesterol crystals into the external carotid artery to form multiple microinfarcts (MMI), animals exhibit reduced cognitive functi…”
BackgroundProtein-protein interactions in neurodegenerative diseases: A conspiracy theory
Thompson, T., Chaggar, P., Ellen Kuhl, A., Goriely, A., & Initiative, A. D. N. (2020) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1008267 · Cited by 97
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“The glymphatic system was first described in rodent brain,(60) and constitutes a paravascular pathway for convective transport of fluids and solutes along the arterial brain vessels, via interstitial tissue and with efflux along the venous brain vessels.(60) The rodent glymphatic system seems to be primarily active du…”
BackgroundKorbecki, A., Zimny, A., Podgórski, P., Sąsiadek, M. J., & Bladowska, J. (2019) · Polish Journal of Radiology · doi:10.5114/pjr.2019.86881 · Cited by 92
Clearance of two organic nanoparticles from the brain via the paravascular pathway
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Glymphatic system: a gateway for neuroinflammation
Zou, K., Deng, Q., Zhang, H., & Huang, C. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.391312 · Cited by 98
“Aβ protein can be transported along the glymphatic pathway in the brain and loss of the AQP4 expression can inhibit Aβ removal, suggesting that the glymphatic system has emerged as a vital player in the net removal of Aβ (Iliff et al., 2012; Xu et al., 2015).”
InfluentialAlzheimer’s disease and its treatment–yesterday, today, and tomorrow
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How astrocyte networks may contribute to cerebral metabolite clearance
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Perivascular space fluid contributes to diffusion tensor imaging changes in white matter
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“It responsible for the clearance of macromolecular and wastes in ISF and CSF out of the CNS [12, 16, 18, 30].”
BackgroundInfluentialTaoka, T., & Naganawa, S. (2020) · Japanese Journal of Radiology · doi:10.1007/s11604-020-01017-0 · Cited by 88
“hypothesized that the cerebrospinal fluid (CSF) and interstitial fluid (ISF) in the perivascular or interstitial spaces within the brain constitute a mass transport system or pathway corresponding to the lymphatic system [1].”
BackgroundInfluentialPresa, J., Saravia, F., Bagi, Z. A., & Filosa, J. A. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.584135 · Cited by 97
“There is some evidence that the absence of AQP4 at the gliovascular interface impairs clearance and transport via the glymphatic system (Iliff et al., 2012, 2013).”
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Stanton, E. H., Persson, N. D. Å., Gomolka, R. S., Lilius, T. O., Sigurðsson, B., Lee, H., Xavier, A. L. R., Benveniste, H., Nedergaard, M., & Mori, Y. (2021) · Magnetic Resonance in Medicine · doi:10.1002/mrm.28645 · Cited by 86
“The 13 VOIs were placed in four representative regions: (1) the infusion site, (2) the subarachnoid space cisterns, (3) the parenchyma, and (4) the clearance pathway (see Results; Table 3).”
MethodResultSelf-citationHigh-altitude cerebral edema: its own entity or end-stage acute mountain sickness?
Turner, R., Gatterer, H., Falla, M., & Lawley, J. S. (2021) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00861.2019 · Cited by 92
Glymphatic dysfunction in isolated REM sleep behavior disorder
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“Then, we preprocessed the DTI data with a DSI studio program as follows22: (1) read the DICOM files and perform a quality inspection; (2) set up a mask to filter out the background region, increase the reconstruction efficacy, and facilitate further visualization; and (3) perform reconstruction with the DTI method to…”
BackgroundMethodBae, Y. J., Kim, J., Choi, B. S., Choi, J.-H., Ryoo, N., Song, Y. S., Cho, S. J., & Kim, J. H. (2023) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2023.105767 · Cited by 88
Glymphatic dysfunction in patients with early-stage amyotrophic lateral sclerosis
Liu, S., Sun, X., Ren, Q., Chen, Y., Dai, T., Yang, Y., Gong, G., Li, W., Zhao, Y., Meng, X., et al. (2023) · Brain · doi:10.1093/brain/awad274 · Cited by 88
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“Dysfunction of the glymphatic system impairs the clearance function and leads to the accumulation of toxic proteins [1, 9].”
Glymphatic dysfunction in Alzheimer’s disease: A critical appraisal
Keil, S. A., Jansson, D., Braun, M., & Iliff, J. J. (2025) · Science · doi:10.1126/science.adv8269 · Cited by 100
Self-citationLactate Shuttling and Lactate use as Fuel after Traumatic Brain Injury: Metabolic Considerations
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Rapid manifestation of reactive astrogliosis in acute hippocampal brain slices
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Self-citationThe Prion-Like Properties of Amyloid-β Assemblies: Implications for Alzheimer's DiseasePreprint
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Plog, B. A., Lou, N., Pierre, C. A., Cove, A., Kenney, H. M., Hitomi, E., Kang, H., Iliff, J. J., Zeppenfeld, D. M., Nedergaard, M., et al. (2019) · Journal of neurosurgery · doi:10.3171/2019.2.jns182675 · Cited by 89
Self-citationImaging the effect of the circadian light–dark cycle on the glymphatic system in awake rats
Cai, X., Qiao, J., Kulkarni, P. P., Harding, I. C., Ebong, E. E., & Ferris, C. F. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1914017117 · Cited by 88
“The CSF is in communication with the ISF of the brain parenchyma via the perivascular system that provides for CSF–ISF exchange of molecules throughout the extracellular fluid compartment (1, 9).”
BackgroundMethodInfluentialVolumetric distribution of perivascular space in relation to mild cognitive impairment
Sepehrband, F., Barisano, G., Sheikh‐Bahaei, N., Choupan, J., Cabeen, R. P., Lynch, K. M., Crawford, M. S., Lan, H., Mack, W. J., Chui, H. C., et al. (2020) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2020.12.010 · Cited by 86
“…(glia-lymphatic) system, whose main pathway is represented by the PVS, is a substantial factor in the net clearance of Aβ (Da Mesquita et al., 2018; Iliff et al., 2012; Louveau et al., 2018; Xu et al., 2015); reduction of efflux of interstitial fluid to the CSF in PVS could lessen Aβ clearance…”
BackgroundMelatonin levels in the Alzheimer’s disease continuum: a systematic review
Nous, A., Engelborghs, S., & Smolders, I. J. (2021) · Alzheimer s Research & Therapy · doi:10.1186/s13195-021-00788-6 · Cited by 87
“Sleep disturbances, such as nightly restlessness and sundowning, according to the glymphatic hypothesis [65, 66], might lead to disease progression by decreased functioning of the”
BackgroundCai, X., Chen, Z., He, C., Zhang, P., Nie, K., Qiu, Y., Wang, L., Wang, L., Jing, P., & Zhang, Y. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.13984 · Cited by 86
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Antibody pharmacokinetics in rat brain determined using microdialysis
Chang, H.-Y., Morrow, K., Bonacquisti, E. E., Zhang, W., & Shah, D. K. (2018) · mAbs · doi:10.1080/19420862.2018.1473910 · Cited by 87
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“Damage to the brain vasculature can lead to loss of perivascular integrity and AQP4 polarization (Iliff et al., 2012), as well as impairment of cerebrovascular pulsatility (Hadaczek et al.”
BackgroundInfluentialApolipoprotein E4 and meningeal lymphatics in Alzheimer disease: a conceptual framework
Mentis, A. A., Dardiotis, E., & Chrousos, G. P. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0731-7 · Cited by 83
“The glymphatic system supports CSF–ISF exchange and clearance of interstitial waste from the brain parenchyma [133], not only in mice, but also in humans [154].”
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Meningeal lymphatic drainage: novel insights into central nervous system disease
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Blood‐brain barrier damage in vascular dementia
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Impaired glymphatic function in idiopathic intracranial hypertension
Eide, P. K., Pripp, A. H., Ringstad, G. A., & Valnes, L. M. (2021) · Brain Communications · doi:10.1093/braincomms/fcab043 · Cited by 85
“Over the last few years, our understanding of CSF homeostasis has changed, not least facilitated by the discovery of the glymphatic system in 2012.(10) From the initial studies performed in rodents, we have learned that in humans a tracer molecule administered to the lumbar CSF enriches around large artery trunks, bef…”
BackgroundInteractions between glial cells and the blood-brain barrier and their role in Alzheimer's disease
Zhao, M., Jiang, X., Zhang, H., Sun, J., Pei, H., Ma, L., Cao, Y., & Li, H. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101483 · Cited by 86
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Open questions for Alzheimer’s disease immunotherapy
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Alzheimer's disease: a mathematical model for onset and progression
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Melatonin Treatment Enhances Aβ Lymphatic Clearance in a Transgenic Mouse Model of Amyloidosis
Pappolla, M. A., Matsubara, E., Vidal, R., Pacheco‐Quinto, J., Pöeggeler, B., Zagorski, M. G., & Sambamurti, K. (2018) · Current Alzheimer Research · doi:10.2174/1567205015666180411092551 · Cited by 83
Cortical interlaminar astrocytes across the therian mammal radiation.
Falcone, C., Wolf‐Ochoa, M., Amina, S., Hong, T., Vakilzadeh, G., Hopkins, W. D., Hof, P. R., Sherwood, C. C., Manger, P. R., Noctor, S. C., et al. (2019) · Journal of Comparative Neurology · doi:10.1002/cne.24605 · Cited by 84
Altered Waste Disposal System in Aging and Alzheimer’s Disease: Focus on Astrocytic Aquaporin-4
Valenza, M., Facchinetti, R., Steardo, L., & Scuderi, C. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01656 · Cited by 90
“Despite these, not all scientists believe that such glymphatic waste system actually exists, at least as presented by Iliff et al. (2012) because of some inconsistent findings suggesting that solute transport does not depend on the astrocytic AQP-4 (Smith et al., 2017; Iliff and Simon, 2019; Smith…”
BackgroundInfluentialTan, H. Y., Cho, H., & Lee, L. P. (2020) · Nature Biomedical Engineering · doi:10.1038/s41551-020-00643-3 · Cited by 87
Petitclerc, L., Hirschler, L., Wells, J. A., Thomas, D. L., van Walderveen, M. A. A., van Buchem, M. A., & van Osch, M. J. P. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118755 · Cited by 81
“Keywords: Arterial Spin Labeling, Blood-CSF barrier, neurofluids, glymphatics, brain clearance, water transport, dynamic compartmental modeling Comment [PL(1]: R3.”
BackgroundPreininger, M. K., & Kaufer, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116217 · Cited by 87
Brain perivascular space imaging across the human lifespan
Lynch, K. M., Sepehrband, F., Toga, A. W., & Choupan, J. (2023) · NeuroImage · doi:10.1016/j.neuroimage.2023.120009 · Cited by 87
“For age effects, Bayesian information criteria (BIC) was used to identify the model that accounts for the most age-related variance in PVS morphology among the following 4 models typically used to characterize lifespan trajectories: (1) linear regression, (2) second-order polynomial model, (3) Poisson curve, and (4) n…”
Advances and controversies in meningeal biology
Betsholtz, C., Engelhardt, B., Koh, G. Y., McDonald, D. M., Proulx, S. T., & Siegenthaler, J. A. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01701-8 · Cited by 91
“…of the SAS into two compartments by a Prox1 + putative barrier-forming fourth meningeal layer has been used to explain how CSF can selectively enter periarteriolar spaces at the origin of a unidirectional waste clearance system for brain macromolecules 25 , referred to as the glymphatic system 87 .”
ECM in brain aging and dementia
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Golanov, E. V., Bovshik, E. I., Wong, K. K., Pautler, R. G., Foster, C. H., Federley, R., Zhang, J. Y., Mancuso, J. J., Wong, S. T. C., & Britz, G. W. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17701157 · Cited by 86
Impact of the Glymphatic System on the Kinetic and Distribution of Gadodiamide in the Rat Brain
Taoka, T., Jošt, G., Frenzel, T., Naganawa, S., & Pietsch, H. (2018) · Investigative Radiology · doi:10.1097/rli.0000000000000473 · Cited by 83
The need for mathematical modelling of spatial drug distribution within the brain
Vendel, E., Rottschäfer, V., & de Lange, E. C. M. (2019) · Fluids and Barriers of the CNS · doi:10.1186/s12987-019-0133-x · Cited by 87
Achieving brain clearance and preventing neurodegenerative diseases—A glymphatic perspective
Kylkilahti, T. M., Berends, E., Ramos, M., Shanbhag, N. C., Töger, J., Bloch, K. M., & Lundgaard, I. (2021) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20982388 · Cited by 91
Bulk flow of cerebrospinal fluid observed in periarterial spaces is not an artifact of injection
Raghunandan, A., Ladrón-de-Guevara, A., Tithof, J., Mestre, H., Du, T., Nedergaard, M., Thomas, J. H., & Kelley, D. H. (2021) · eLife · doi:10.7554/elife.65958 · Cited by 86
Self-citationRecent insights on astrocyte mechanisms in CNS homeostasis, pathology, and repair
Hart, C. G., & Karimi‐Abdolrezaee, S. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24922 · Cited by 88
Tumor‐targeted nanotherapeutics: overcoming treatment barriers for glioblastoma
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Arterial Pulsations cannot Drive Intramural Periarterial Drainage: Significance for Aβ Drainage
Diem, A. K., Sharp, M. M., Gatherer, M., Bressloff, N. W., Carare, R. O., & Richardson, G. W. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00475 · Cited by 87
Extracellular Tau and Its Potential Role in the Propagation of Tau Pathology
Yamada, K. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00667 · Cited by 86
A Rationally Designed Humanized Antibody Selective for Amyloid Beta Oligomers in Alzheimer’s Disease
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Bypassing the blood-brain barrier
Rustenhoven, J., & Kipnis, J. (2019) · Science · doi:10.1126/science.aay0479 · Cited by 82
The role of glymphatic system in the cerebral edema formation after ischemic stroke
Ji, C., Yu, X., Xu, W., Lenahan, C., Tu, S., & Shao, A. (2021) · Experimental Neurology · doi:10.1016/j.expneurol.2021.113685 · Cited by 82
DAMPs and RAGE Pathophysiology at the Acute Phase of Brain Injury: An Overview
Balança, B., Desmurs, L., Grelier, J., Perret‐Liaudet, A., & Lukaszewicz, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052439 · Cited by 87
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“For instance, the glymphatic system, a brain-wide network of perivascular spaces responsible for waste clearance, is influenced by sleep patterns and possibly modulated by n-3 PUFAs (Iliff et al., 2012).”
BackgroundEisma, J. J., McKnight, C. D., Hett, K., Elenberger, J., Han, C., Song, A. K., Considine, C. M., Claassen, D. O., & Donahue, M. J. (2024) · Fluids and Barriers of the CNS · doi:10.1186/s12987-024-00525-9 · Cited by 94
“…choroid plexus is widely believed to be the primary source of CSF production in the brain, producing CSF at a rate of 430–530 mL/day [1], and the choroid plexus has gained additional recent attention owing to its role as one of the most proximal components of the brain’s waste clearance system [2].”
BackgroundFunctional analysis of the human perivascular subarachnoid space
Eide, P. K., & Ringstad, G. A. (2024) · Nature Communications · doi:10.1038/s41467-024-46329-1 · Cited by 85
Glial fibrillary acidic protein in Alzheimer’s disease: a narrative review
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“134 This system is essential for clearing the brain of metabolic waste and potentially harmful substances.”
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Neurogenetic basis for circadian regulation of metabolism by the hypothalamusPreprint
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Mouse models of neurodegeneration: Know your question, know your mouse
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“Some theories posit that A (cid:2) plaque deposition results from upstream dysfunction of the lifelong role of astrocytes in A (cid:2) processing and clearance [27–29], including mechanisms associated with the glym-phatic system [27, 30].”
The mechanisms behind perivascular fluid flow
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Microvascular Alterations in Alzheimer's Disease
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“This CSF-ISF mixture, via bulk flow or diffusion, travels through the tissue and is eliminated along paravascular spaces surrounding veins (Iliff et al., 2012; Reeves et al., 2020).”
Background
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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