Perivascular spaces, glymphatic dysfunction, and small vessel disease
Open accessAbstract
Cerebral small vessel diseases (SVDs) range broadly in etiology but share remarkably overlapping pathology. Features of SVD including enlarged perivascular spaces (EPVS) and formation of abluminal protein deposits cannot be completely explained by the putative pathophysiology. The recently discovered glymphatic system provides a new perspective to potentially address these gaps. This work provides a comprehensive review of the known factors that regulate glymphatic function and the disease mechanisms underlying glymphatic impairment emphasizing the role that aquaporin-4 (AQP4)-lined perivascular spaces (PVSs), cerebrovascular pulsatility, and metabolite clearance play in normal CNS physiology. This review also discusses the implications that glymphatic impairment may have on SVD inception and progression with the aim of exploring novel therapeutic targets and highlighting the key questions that remain to be answered.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Sleep quality is compromised in cardiovascular diseases, perhaps providing a link to impaired glymphatic clearance and subsequent protein aggregation and dementia.
“It is also well-establish that the quality of sleep is compromised in cardiovascular diseases (93) perhaps providing a link to impaired glymphatic clearance and subsequent protein aggregation and dementia (94).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [94]
Hypertension induces hypertrophy of vascular smooth muscle cells and arterial wall stiffening, dampening pulsatility and compliance, reducing convective perivascular flow.
“Hypertension in particular induces hypertrophy of vascular smooth muscle cells, with a stiffening of the arterial wall that dampens arterial wall pulsatility and compliance, thus reducing convective perivascular flow (94, 100).”
From Glymphatic failure as a final common pathway to dementia (2020) · cites this paper as [94]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., Benveniste, H., Vates, G. E., Deane, R., Goldman, S. A., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003748 · Cited by 5,824 · see citing works
Self-citationWardlaw, J. M., Smith, E. E., Biessels, G. J., Cordonnier, C., Fazekas, F., Frayne, R., Lindley, R. I., O'Brien, J. T., Barkhof, F., Benavente, O. R., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70124-8 · Cited by 5,560 · 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-citationStructural and functional features of central nervous system lymphatic vessels
Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., Derecki, N. C., Castle, D., Mandell, J. W., Lee, K. S., et al. (2015) · Nature · doi:10.1038/nature14432 · Cited by 4,413 · see citing works
Pantoni, L. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70104-6 · Cited by 3,405 · 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 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-citationNotch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia
Joutel, A., Corpechot, C., Ducros, A., Vahedi, K., Chabriat, H., Mouton, P., Alamowitch, S., Domenga, V., Cécillion, M., Maréchal, E., et al. (1996) · Nature · doi:10.1038/383707a0 · Cited by 2,068 · see citing works
Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging
Wardlaw, J. M., Smith, C., & Dichgans, M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70060-7 · Cited by 1,657 · see citing works
Impairment 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 · cited 6× · see citing works
“A loss in compliance would be expected to result in an increase in pulsatility, counter to the results seen in old mice(28).”
BackgroundMethodResultInfluentialSelf-citationNielsen, 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
Strittmatter, W. J., Weisgraber, K. H., Huang, D. Y., Dong, L. M., Salvesen, G. S., Pericak-Vance, M., Schmechel, D., Saunders, A. M., Goldgaber, D., & Roses, A. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.17.8098 · Cited by 1,363 · 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-citationSafar, M. E., Levy, B. I., & Struijker-Boudier, H. A. J. (2003) · Circulation · doi:10.1161/01.cir.0000069826.36125.b4 · Cited by 1,195 · see citing works
Taoka, 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-citationBrain-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-citationChabriat, H., Joutel, A., Dichgans, M., Tournier-Lasserve, E., & Bousser, M.-G. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70127-9 · Cited by 1,088 · see citing works
Mathiisen, T. M., Lehre, K. P., Danbolt, N. C., & Ottersen, O. P. (2010) · Glia · doi:10.1002/glia.20990 · Cited by 917 · see citing works
Enlarged perivascular spaces on MRI are a feature of cerebral small vessel disease
Doubal, F. N., MacLullich, A. M. J., Ferguson, K. J., Dennis, M. S., & Wardlaw, J. M. (2010) · Stroke · doi:10.1161/strokeaha.109.564914 · Cited by 904 · see citing works
apoE isoform–specific disruption of amyloid β peptide clearance from mouse brain
Deane, R., Sagare, A., Hamm, K., Parisi, M., Lane, S., Finn, M. B., Holtzman, D. M., & Zlokovic, B. V. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36663 · Cited by 771 · see citing works
Aquaporin‐4 facilitates reabsorption of excess fluid in vasogenic brain edema
Papadopoulos, M. C., Manley, G. T., Krishna, S., & Verkman, A. S. (2004) · The FASEB Journal · doi:10.1096/fj.04-1723fje · Cited by 749 · see citing works
Nedergaard, M. (2013) · Science · doi:10.1126/science.1240514 · Cited by 704 · see citing works
Self-citationCerebral amyloid angiopathy without and with cerebral hemorrhages: A comparative histological study
Vonsattel, J. P. G., Myers, R. H., Tessa Hedley‐Whyte, E., Ropper, A. H., Bird, E. D., & Richardson, E. P. (1991) · Annals of Neurology · doi:10.1002/ana.410300503 · Cited by 662 · 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
The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients
Joutel, A., Andreux, F., Gaulis, S., Domenga, V., Cécillon, M., Battail‐Poirot, N., Piga, N., Chapon, F., Godfrain, C., & Tournier‐Lasserve, E. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8047 · Cited by 601 · 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-citationJohnston, 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
Notch3 is required for arterial identity and maturation of vascular smooth muscle cellsPreprint
Domenga, V., Fardoux, P., Lacombe, P. M., Monet, M., Maciazek, J., Krebs, L. T., Klonjkowski, B., Berrou, E., Mericskay, M., Li, Z., et al. (2004) · Genes & Development · doi:10.1101/gad.308904 · Cited by 537 · 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-citationApolipoprotein E ϵ4 and cerebral hemorrhage associated with amyloid angiopathy
Greenberg, S. M., Rebeck, G., Vonsattel, J. P., Gómez-Isla, T., & Hyman, B. (1995) · Annals of Neurology · doi:10.1002/ana.410380219 · Cited by 508 · see citing works
Deletion 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
Potter, G. M., Chappell, F. M., Morris, Z., & Wardlaw, J. M. (2015) · Cerebrovascular Diseases · doi:10.1159/000375153 · Cited by 500 · see citing works
Lymphatic drainage of the brain and the pathophysiology of neurological disease
Weller, R. O., Djuanda, E., Yow, H.-Y., & Carare, R. O. (2009) · Acta Neuropathologica · doi:10.1007/s00401-008-0457-0 · Cited by 488 · 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-citationKiviniemi, V. J., Wang, X., Korhonen, V. O., Keinänen, T., Tuovinen, T., Autio, J. A., LeVan, P., Keilholz, S. D., Zang, Y., Hennig, J., et al. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x15622047 · Cited by 443 · see citing works
Self-citationImpaired Glymphatic Perfusion After Strokes Revealed by Contrast-Enhanced MRI
Gaberel, T., Gakuba, C., Goulay, R., de Lizarrondo, S. M., Hanouz, J., Emery, É., Touzé, E., Vivien, D., & Gauberti, M. (2014) · Stroke · doi:10.1161/strokeaha.114.006617 · Cited by 434 · see citing works
Ultrastructural analysis of adult mouse neocortex comparing aldehyde perfusion with cryo fixation
Korogod, N., Petersen, C. C., & Knott, G. W. (2015) · eLife · doi:10.7554/elife.05793 · Cited by 408 · see citing works
Thal, D. R., Ghebremedhin, E., Orantes, M., & Wiestler, O. D. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.12.1287 · Cited by 384 · see citing works
Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism
Lundgaard, I., Li, B., Xie, L., Kang, H., Sanggaard, S., Haswell, J. D. R., Sun, W., Goldman, S., Blekot, S., Nielsen, M., et al. (2015) · Nature Communications · doi:10.1038/ncomms7807 · Cited by 381 · see citing works
Self-citationBlack, S., Gao, F., & Bilbao, J. (2009) · Stroke · doi:10.1161/strokeaha.108.537704 · Cited by 379 · see citing works
Joutel, A., Monet-Leprêtre, M., Gosele, C., Baron-Menguy, C., Hammes, A., Schmidt, S., Lemaire-Carrette, B., Domenga, V., Schedl, A., Lacombe, P., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39733 · Cited by 379 · see citing works
He, X.-F., Liu, D.-X., Zhang, Q., Liang, F.-Y., Dai, G.-Y., Zeng, J.-S., Pei, Z., Xu, G.-Q., & Lan, Y. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00144 · Cited by 371 · see citing works
Is There a Cerebral Lymphatic System?
Iliff, J. J., & Nedergaard, M. (2013) · Stroke · doi:10.1161/strokeaha.112.678698 · Cited by 366 · see citing works
Self-citationDrainage 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
Differences Between Vascular and Plaque Core Amyloid in Alzheimer's Disease
Prelli, F., Castaño, E. M., Glenner, G. G., & Frangione, B. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb01087.x · Cited by 351 · see citing works
Premkumar, D. R., Cohen, D., Hedera, P., Friedland, R. P., & Kalaria, R. N. (1996) · Europe PMC (PubMed Central) · Cited by 345 · 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
Zhu, Y.-C., Tzourio, C., Soumaré, A., Mazoyer, B., Dufouil, C., & Chabriat, H. (2010) · Stroke · doi:10.1161/strokeaha.110.591586 · Cited by 335 · see citing works
Efflux 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 · see citing works
Yang, L., Kress, B. T., Weber, H. J., Thiyagarajan, M., Wang, B., Deane, R., Benveniste, H., Iliff, J. J., & Nedergaard, M. (2013) · Journal of Translational Medicine · doi:10.1186/1479-5876-11-107 · Cited by 317 · see citing works
Self-citationRen, Z., Iliff, J. J., Yang, L., Yang, J., Chen, X., Chen, M. J., Giese, R. N., Wang, B., Shi, X., & Nedergaard, M. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.30 · Cited by 314 · see citing works
Self-citationHadaczek, 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
Impairment of the glymphatic system after diabetes
Jiang, Q., Zhang, L., Ding, G., Davoodi-Bojd, E., Li, Q., Li, L., Sadry, N., Nedergaard, M., Chopp, M., & Zhang, Z. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16654702 · Cited by 308 · see citing works
Self-citationGlymphatic clearance controls state-dependent changes in brain lactate concentration
Lundgaard, I., Lu, M. L., Yang, E., Peng, W., Mestre, H., Hitomi, E., Deane, R., & Nedergaard, M. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16661202 · Cited by 299 · see citing works
Self-citationEnlarged Perivascular Spaces and Cerebral Small Vessel Disease
Potter, G. M., Doubal, F. N., Jackson, C. A., Chappell, F. M., Sudlow, C. L., Dennis, M. S., & Wardlaw, J. M. (2015) · International Journal of Stroke · doi:10.1111/ijs.12054 · Cited by 296 · see citing works
Mechanisms 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
Braffman, B. H., Zimmerman, R. A., Trojanowski, J. Q., Gonatas, N. K., Hickey, W., & Schlaepfer, W. W. (1988) · American Journal of Roentgenology · doi:10.2214/ajr.151.3.551 · Cited by 289 · see citing works
Glymphatic solute transport does not require bulk flow
Asgari, M., de Zélicourt, D., & Kurtcuoglu, V. (2016) · Scientific Reports · doi:10.1038/srep38635 · Cited by 280 · see citing works
Fryer, J. D., Simmons, K., Parsadanian, M., Bales, K. R., Paul, S. M., Sullivan, P. M., & Holtzman, D. M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5170-04.2005 · Cited by 278 · see citing works
Schain, A. J., Melo‐Carrillo, A., Strassman, A. M., & Burstein, R. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.3390-16.2017 · Cited by 254 · see citing works
White matter lesions, cognition, and recurrent hemorrhage in lobar intracerebral hemorrhage
Smith, E. E., Gurol, M. E., Eng, J. A., Engel, C., Nguyen, T. N., Rosand, J. M., & Greenberg, S. M. (2004) · Neurology · doi:10.1212/01.wnl.0000142966.22886.20 · Cited by 252 · see citing works
Achariyar, T. M., Li, B., Peng, W., Verghese, P. B., Shi, Y., McConnell, E., Benraiss, A., Kasper, T., Song, W., Takano, T., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0138-8 · Cited by 250 · see citing works
Self-citationWilcock, D. M., Vitek, M. P., & Colton, C. A. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.01.023 · Cited by 249 · see citing works
Cerebrospinal Fluid Clearance in Alzheimer Disease Measured with Dynamic PET
de Leon, M. J., Li, Y., Okamura, N., Tsui, W. H., Saint-Louis, L. A., Glodzik, L., Osorio, R. S., Fortea, J., Butler, T., Pirraglia, E., et al. (2017) · Journal of Nuclear Medicine · doi:10.2967/jnumed.116.187211 · Cited by 246 · see citing works
Self-citationCarnevale, D., Mascio, G., D'Andrea, I., Fardella, V., Bell, R. D., Branchi, I., Pallante, F., Zlokovic, B., Yan, S. S., & Lembo, G. (2012) · Hypertension · doi:10.1161/hypertensionaha.112.195511 · Cited by 241 · see citing works
Loss of Astrocyte Polarization in the Tg-ArcSwe Mouse Model of Alzheimer's Disease
Yang, J., Lunde, L. K., Nuntagij, P., Oguchi, T., Camassa, L. M. A., Nilsson, L. N. G., Lannfelt, L., Xu, Y., Amiry-Moghaddam, M. R., Ottersen, O. P., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110725 · Cited by 228 · see citing works
The enigma of vascular cognitive disorder and vascular dementia
Jellinger, K. A. (2007) · Acta Neuropathologica · doi:10.1007/s00401-006-0185-2 · Cited by 221 · see citing works
Perivascular spaces in the basal ganglia of the human brain: their relationship to lacunes
POLLOCK, H., HUTCHINGS, M., WELLER, R. O., & ZHANG, E. (1997) · Journal of Anatomy · doi:10.1046/j.1469-7580.1997.19130337.x · Cited by 220 · see citing works
Monet, M., Haddad, I., Baron‐Menguy, C., Panchal, M., Riani, M., Domenga, V., Dussaule, C., Cognat, E., Vinh, J., & Joutel, A. (2013) · Brain · doi:10.1093/brain/awt092 · Cited by 220 · see citing works
Eide, P. K., & Ringstad, G. (2015) · Acta Radiologica Open · doi:10.1177/2058460115609635 · Cited by 218 · see citing works
Large and Small Artery Cross-Talk and Recent Morbidity-Mortality Trials in Hypertension
Laurent, S., Briet, M., & Boutouyrie, P. (2009) · Hypertension · doi:10.1161/hypertensionaha.109.133116 · Cited by 217 · see citing works
Distribution 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 · see citing works
Paravascular microcirculation facilitates rapid lipid transport and astrocyte signaling in the brain
Thrane, V. R., Thrane, A. S., Plog, B. A., Thiyagarajan, M., Iliff, J. J., Deane, R., Nagelhus, E. A., & Nedergaard, M. (2013) · Scientific Reports · doi:10.1038/srep02582 · Cited by 213 · see citing works
Self-citationMidlife Blood Pressure, Plasma β-Amyloid, and the Risk for Alzheimer Disease
Shah, N. S., Vidal, J., Masaki, K., Petrovitch, H., Ross, G. W., Tilley, C., Demattos, R. B., Tracy, R. P., White, L. R., & Launer, L. J. (2012) · Hypertension · doi:10.1161/hypertensionaha.111.178962 · Cited by 212 · see citing works
Bradbury, 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
Jin, B.-J., Smith, A. J., & Verkman, A. S. (2016) · Journal of General Physiology · doi:10.1085/jgp.201611684 · Cited by 204 · see citing works
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 195 · see citing works
Self-citationCognitive Deficits and Delayed Neuronal Loss in a Mouse Model of Multiple Microinfarcts
Wang, M., Iliff, J. J., Liao, Y., Chen, M. J., Shinseki, M. S., Venkataraman, A., Cheung, J., Wang, W., & Nedergaard, M. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1860-12.2012 · Cited by 183 · see citing works
Self-citationGhosh, M., Balbi, M., Hellal, F., Dichgans, M., Lindauer, U., & Plesnila, N. (2015) · Annals of Neurology · doi:10.1002/ana.24512 · Cited by 171 · see citing works
Charidimou, A., Pantoni, L., & Love, S. (2015) · International Journal of Stroke · doi:10.1177/1747493015607485 · Cited by 168 · see citing works
Transcranial Doppler Pulsatility Indices as a Measure of Diffuse Small‐Vessel Disease
Kidwell, C. S., El-Saden, S. M., Livshits, Z., Martin, N. A., Glenn, T. C., & Saver, J. L. (2001) · Journal of Neuroimaging · doi:10.1111/j.1552-6569.2001.tb00039.x · Cited by 160 · see citing works
Obstructive sleep apnea decreases central nervous system–derived proteins in the cerebrospinal fluid
Ju, Y. S., Finn, M. B., Sutphen, C. L., Herries, E. M., Jerome, G. M., Ladenson, J. H., Crimmins, D. L., Fagan, A. M., & Holtzman, D. M. (2016) · Annals of Neurology · doi:10.1002/ana.24672 · Cited by 160 · see citing works
Neuropathological correlates of temporal pole white matter hyperintensities in CADASIL
Yamamoto, Y., Ihara, M., Tham, C., Low, R. W. C., Slade, J. Y., Moss, T., Oakley, A. E., Polvikoski, T., & Kalaria, R. N. (2009) · Stroke · doi:10.1161/strokeaha.108.528299 · Cited by 155 · cited 1× · see citing works
“Despite having relatively distinct etiologies, EPVS are widespread and present in almost all SVD types, it is an established observation in both sporadic type 1and 2 and hereditary type 2 and 3 forms of SVD(40, 44, 45).”
BackgroundEmerging Evidence for Pathogenesis of Sporadic Cerebral Small Vessel Disease
Ihara, M., & Yamamoto, Y. (2016) · Stroke · doi:10.1161/strokeaha.115.009627 · 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
Aquaporin Expression in the Brains of Patients With or Without Cerebral Amyloid Angiopathy
Moftakhar, P., Lynch, M. D., Pomakian, J., & Vinters, H. V. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181fd252c · Cited by 136 · see citing works
Baydaş, G., Nedzvetsky, V. S., Tuzcu, M., Yaşar, A., & Кириченко, С. В. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01294-9 · Cited by 135 · see citing works
Gd-based Contrast Enhancement of the Perivascular Spaces in the Basal Ganglia
Naganawa, S., Nakane, T., Kawai, H., & Taoka, T. (2016) · Magnetic Resonance in Medical Sciences · doi:10.2463/mrms.mp.2016-0039 · Cited by 130 · see citing works
Venkat, P., Chopp, M., Zacharek, A., Cui, C., Zhang, L., Li, Q., Lü, M., Zhang, T., Liu, A., & Chen, J. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.11.002 · Cited by 128 · 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
Joutel, A., & Faraci, F. M. (2014) · Stroke · doi:10.1161/strokeaha.113.002878 · Cited by 113 · see citing works
Genetic factors in cerebral small vessel disease and their impact on stroke and dementia
Haffner, C., Malik, R., & Dichgans, M. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.71 · Cited by 109 · see citing works
Co-aggregate formation of CADASIL-mutant NOTCH3: a single-particle analysis
Duering, M., Karpinska, A., Rosner, S., Hopfner, F., Zechmeister, M., Peters, N., Kremmer, E., Haffner, C., Giese, A., Dichgans, M., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr237 · Cited by 106 · see citing works
Johnston, M., Zakharov, A., Koh, L., & Armstrong, D. W. (2005) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2005.00679.x · Cited by 106 · see citing works
Virchow-Robin Spaces: Correlations with Polysomnography-Derived Sleep Parameters
Berezuk, C., Ramirez, J., Gao, F., Scott, C. J. M., Huroy, M., Swartz, R. H., Murray, B. J., Black, S. E., & Boulos, M. I. (2015) · SLEEP · doi:10.5665/sleep.4726 · Cited by 102 · see citing works
Clearance from the mouse brain by convection of interstitial fluid towards the ventricular system
Bedussi, B., van Lier, M. G. J. T. B., Bartstra, J. W., de Vos, J., Siebes, M., VanBavel, E., & Bakker, E. N. T. P. (2015) · Fluids and Barriers of the CNS · doi:10.1186/s12987-015-0019-5 · Cited by 102 · see citing works
Moore, D. F., Altarescu, G., Barker, W. C., Patronas, N. J., Herscovitch, P., & Schiffmann, R. (2003) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2003.09.021 · Cited by 101 · see citing works
Nozaki, H., Nishizawa, M., & Onodera, O. (2014) · Stroke · doi:10.1161/strokeaha.114.004236 · Cited by 97 · see citing works
Moderate-to-severe obstructive sleep apnea is associated with cerebral small vessel disease
Song, T., Park, J., Choi, K. H., Chang, Y., Moon, J., Kim, J., Choi, Y., Kim, Y., & Lee, H. W. (2016) · Sleep Medicine · doi:10.1016/j.sleep.2016.03.006 · Cited by 97 · see citing works
Notch signalling in smooth muscle cells during development and disease
Fouillade, C., Monet, M., Baron‐Menguy, C., & Joutel, A. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs019 · Cited by 94 · see citing works
Dabertrand, F., Krøigaard, C., Bonev, A. D., Cognat, E., Dalsgaard, T., Domenga, V., Hill‐Eubanks, D. C., Brayden, J. E., Joutel, A., & Nelson, M. T. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1420765112 · Cited by 94 · see citing works
Mechanical stress activates NMDA receptors in the absence of agonists
Maneshi, M. M., Maki, B. A., Gnanasambandam, R., Belin, S., Popescu, G., Sachs, F., & Hua, S. Z. (2017) · Scientific Reports · doi:10.1038/srep39610 · Cited by 92 · see citing works
Reducing T imp3 or vitronectin ameliorates disease manifestations in CADASIL mice
Capone, C., Cognat, E., Ghezali, L., Baron‐Menguy, C., Aubin, D., Mesnard, L., Stöhr, H., Domenga, V., Nelson, M. T., & Joutel, A. (2015) · Annals of Neurology · doi:10.1002/ana.24573 · Cited by 90 · see citing works
Risk Factors for Cerebral Amyloid Angiopathy in the Elderly
Yamada, M. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04797.x · Cited by 88 · see citing works
Yamamoto, Y., Craggs, L., Watanabe, A., Booth, T. A., Attems, J., Low, R. W. C., Oakley, A. E., & Kalaria, R. N. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31829020b5 · Cited by 85 · see citing works
Hereditary cerebral small vessel diseases: a review
Federico, A., Di Donato, I., Bianchi, S., Di Palma, C., Taglia, I., & Dotti, M. T. (2012) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2012.07.041 · Cited by 82 · see citing works
White Matter Lesions and Dementia MRI‐Pathological Correlation
Udaka, F., Sawada, H., & Kameyama, M. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04845.x · Cited by 81 · see citing works
Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain
Murlidharan, G., Crowther, A., Reardon, R. A., Song, J., & Asokan, A. (2016) · JCI Insight · doi:10.1172/jci.insight.88034 · Cited by 72 · see citing works
Stroke and Potentially Preventable Dementias Proclamation: Updated World Stroke Day Proclamation
Hachinski, V. (2015) · Stroke · doi:10.1161/strokeaha.115.011237 · Cited by 71 · see citing works
Dilated perivascular spaces in small-vessel disease: a study in CADASIL
Yao, M., Hervé, D., Jouvent, E., Duering, M., Reyes, S., Godin, O., Guichard, J. P., Dichgans, M., & Chabriat, H. (2014) · Cerebrovascular Diseases · doi:10.1159/000356982 · Cited by 71 · see citing works
Brutto, Ó. H. D., Mera, R. M., Zambrano, M., Lama, J., Brutto, V. J. D., & Castillo, P. R. (2015) · Sleep Medicine · doi:10.1016/j.sleep.2014.10.023 · Cited by 68 · see citing works
Tomassoni, D., Avola, R., Tullio, M. A. D., Sabbatini, M., Vitaioli, L., & Amenta, F. (2004) · Clinical and Experimental Hypertension · doi:10.1081/ceh-120034138 · Cited by 68 · see citing works
Vasopressin-dependent short-term regulation of aquaporin 4 expressed in Xenopus oocytes
Moeller, H. B., Fenton, R. A., Zeuthen, T., & MacAulay, N. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.09.072 · Cited by 61 · see citing works
Expression of aquaporins 1 and 4 in the brain of spontaneously hypertensive rats
Tomassoni, D., Bramanti, V., & Amenta, F. (2010) · Brain Research · doi:10.1016/j.brainres.2010.02.023 · Cited by 59 · see citing works
Expression of Aquaporin 4 and Kir4.1 in Diabetic Rat Retina: Treatment with Minocycline
Zhang, Y., Xu, G., Ling, Q., & Da, C. (2011) · Journal of International Medical Research · doi:10.1177/147323001103900214 · Cited by 59 · see citing works
Cognat, E., Cléophax, S., Domenga, V., & Joutel, A. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-49 · Cited by 57 · see citing works
Ghorbani, A., Ahmadi, M., & Shemshaki, H. (2015) · Advanced Biomedical Research · doi:10.4103/2277-9175.151574 · Cited by 53 · see citing works
ISHIDA, H., Takemori, K., Dote, K., & Ito, H. (2006) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2005.06.023 · Cited by 48 · see citing works
Biochemical Characterization and Cellular Effects of CADASIL Mutants of NOTCH3
Meng, H., Zhang, X., Yu, G., Lee, S. J., Chen, Y. E., Prudovsky, I. A., & Wang, M. M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044964 · Cited by 46 · see citing works
Loos, C., Klarenbeek, P., van Oostenbrugge, R. J., & Staals, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137323 · Cited by 42 · see citing works
Pavlovic, A. M., Pekmezovic, T. D., Trajković, J. Z., Švabić, T., Veselinovic, N., Radojičić, A., Mijajlovic, M. D., Tomić, G., Jovanović, Z., Norton, M., et al. (2015) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4289 · Cited by 37 · see citing works
Microvasculature of the human cerebral meninges
Nonaka, H., Akima, M., Nagayama, T., Hatori, T., Zhang, Z., & Ihara, F. (2003) · Neuropathology · doi:10.1046/j.1440-1789.2003.00487.x · Cited by 33 · see citing works
Cheng, C.-Y., Tsai, C.-F., Wang, S., Hsu, C., & Fuh, J. (2013) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988713493503 · Cited by 30 · see citing works
PERIVENTRICULAR WHITE MATTER LESIONS AND SLEEP ALTERATION IN OLDER PEOPLE
Kanda, A., Matsui, T., Ebihara, S., Arai, H., & Sasaki, H. (2003) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2003.51125.x · Cited by 27 · see citing works
Flagged first, then by citations
1 of the 127 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The 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-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-citationβ-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
Cannistraro, R. J., Badi, M. K., Eidelman, B. H., Dickson, D. W., Middlebrooks, E. H., & Meschia, J. F. (2019) · Neurology · doi:10.1212/wnl.0000000000007654 · Cited by 655 · 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-citationRasmussen, M. K., Mestre, H., & Nedergaard, M. (2021) · Physiological Reviews · doi:10.1152/physrev.00031.2020 · Cited by 622 · see citing works
Self-citationBrain-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
“This enlargement may therefore reduce resistance to perivascular tracer influx (76).”
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 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
Self-citationUnderstanding the role of the perivascular space in cerebral small vessel disease
Brown, R., Benveniste, H., Black, S. E., Charpak, S., Dichgans, M., Joutel, A., Nedergaard, M., Smith, K. J., Zloković, B. V., & Wardlaw, J. M. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy113 · Cited by 342 · see citing works
Self-citationInoue, Y., Shue, F., Bu, G., & Kanekiyo, T. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00640-5 · Cited by 356 · see citing works
The glymphatic hypothesis: the theory and the evidence
Hladky, S. B., & Barrand, M. A. (2022) · Fluids and Barriers of the CNS · doi:10.1186/s12987-021-00282-z · Cited by 271 · see citing works
The glymphatic system: implications for drugs for central nervous system diseases
Lohela, T. J., Lilius, T. O., & Nedergaard, M. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00500-9 · Cited by 246 · see citing works
Self-citationNon-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes
Albayram, S., Smith, G., Tufan, F., Tuna, İ. S., Bostancıklıoğlu, M., Zile, M. R., & Albayram, Ö. (2022) · Nature Communications · doi:10.1038/s41467-021-27887-0 · Cited by 239 · see citing works
Cognitive impact of COVID-19: looking beyond the short term
Miners, J. S., Kehoe, P. G., & Love, S. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00744-w · Cited by 248 · see citing works
The Neuroprotective Effects of Exercise: Maintaining a Healthy Brain Throughout Aging
Vecchio, L. M., Meng, Y., Xhima, K., Lipsman, N., Hamani, C., & Aubert, I. (2018) · Brain Plasticity · doi:10.3233/bpl-180069 · Cited by 230 · see citing works
Shen, T., Yue, Y., Ba, F., He, T., Tang, X., Hu, X., Pu, J., Huang, C., Lv, W., Zhang, B., et al. (2022) · npj Parkinson s Disease · doi:10.1038/s41531-022-00437-1 · Cited by 214 · see citing works
Interaction between blood-brain barrier and glymphatic system in solute clearance
Verheggen, I. C. M., van Boxtel, M. P. J., Verhey, F. R. J., Jansen, J. F. A., & Backes, W. H. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.03.028 · Cited by 170 · see citing works
Perosa, V., Oltmer, J., Munting, L. P., Freeze, W. M., Auger, C. A., Scherlek, A. A., van der Kouwe, A. J. W., Iglesias, J. E., Atzeni, A., Bacskai, B. J., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02393-1 · Cited by 161 · see citing works
Gouveia-Freitas, K., & de Bastos-Leite, A. J. (2021) · Neuroradiology · doi:10.1007/s00234-021-02718-7 · Cited by 161 · see citing works
Shi, Y., Thrippleton, M. J., Blair, G. W., Dickie, D. A., Marshall, I., Hamilton, I. F., Doubal, F., Chappell, F. M., & Wardlaw, J. M. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x18803956 · Cited by 142 · see citing works
Emerging links between cerebrovascular and neurodegenerative diseases—a special role for pericytes
Lendahl, U., Nilsson, P., & Betsholtz, C. (2019) · EMBO Reports · doi:10.15252/embr.201948070 · Cited by 141 · see citing works
Hippocampal vascular reserve associated with cognitive performance and hippocampal volume
Perosa, V., Priester, A., Ziegler, G., Cárdenas‐Blanco, A., Dobisch, L., Spallazzi, M., Assmann, A., Maaß, A., Speck, O., Oltmer, J., et al. (2019) · Brain · doi:10.1093/brain/awz383 · Cited by 141 · see citing works
Hong, H., Hong, L., Luo, X., Zeng, Q., Li, K., Wang, S., Jiaerken, Y., Zhang, R., Yu, X., Zhang, Y., et al. (2024) · Alzheimer s Research & Therapy · doi:10.1186/s13195-024-01407-w · Cited by 135 · see citing works
Vinje, V., Ringstad, G. A., Lindstrøm, E. K., Valnes, L. M., Rognes, M. E., Eide, P. K., & Mardal, K. (2019) · Scientific Reports · doi:10.1038/s41598-019-46055-5 · Cited by 127 · see citing works
Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease
Duperron, M., Knol, M. J., Grand, Q. L., Evans, T. E., Mishra, A., Tsuchida, A., Roshchupkin, G. V., Konuma, T., Trégouët, D., Romero, J. R., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02268-w · Cited by 130 · see citing works
Direct Measurement of Cerebrospinal Fluid Production in Mice
Liu, G., Mestre, H., Sweeney, A. M., Sun, Q., Weikop, P., Du, T., & Nedergaard, M. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108524 · Cited by 129 · see citing works
Self-citationGlymphatics visualization after focused ultrasound-induced blood-brain barrier opening in humans
Meng, Y., Abrahao, A., Heyn, C. C., Bethune, A. J., Huang, Y., Pople, C. B., Aubert, I., Hamani, C., Zinman, L., Hynynen, K., et al. (2019) · Annals of Neurology · doi:10.1002/ana.25604 · Cited by 114 · see citing works
Association of Dilated Perivascular Spaces With Cognitive Decline and Incident Dementia
Paradise, M., Crawford, J. D., Lam, B. C. P., Wen, W. X., Kochan, N. A., Makkar, S. R., Dawes, L. C., Trollor, J. N., Draper, B., Brodaty, H., et al. (2021) · Neurology · doi:10.1212/wnl.0000000000011537 · Cited by 125 · see citing works
Liu, X., Barisano, G., Shao, X., Jann, K., Ringman, J. M., Lu, H., Arfanakis, K., Caprihan, A., DeCarli, C. S., Gold, B. T., et al. (2023) · Aging and Disease · doi:10.14336/ad.2023.0321-2 · Cited by 123 · see citing works
Lundgaard, I., Wang, W., Eberhardt, A., Vinitsky, H. S., Reeves, B. C., Peng, S., Lou, N., Hussain, R., & Nedergaard, M. (2018) · Scientific Reports · doi:10.1038/s41598-018-20424-y · Cited by 127 · see citing works
Self-citationLoss of perivascular aquaporin‐4 in idiopathic normal pressure hydrocephalus
Hasan‐Olive, M. M., Enger, R., Hansson, H., Nagelhus, E. A., & Eide, P. K. (2018) · Glia · doi:10.1002/glia.23528 · Cited by 118 · see citing works
Mehta, R. I., Carpenter, J. S., Mehta, R. I., Haut, M. W., Ranjan, M., Najib, U., Lockman, P., Wang, P., D’haese, P.-F., & Rezai, A. R. (2021) · Radiology · doi:10.1148/radiol.2021200643 · Cited by 115 · see citing works
Self-citationPerivascular Spaces, Glymphatic System and MR
Yu, L., Hu, X., Li, H., & Zhao, Y. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.844938 · Cited by 114 · see citing works
Body mass index, time of day and genetics affect perivascular spaces in the white matter
Barisano, G., Sepehrband, F., Sheikh‐Bahaei, N., Law, M., & Toga, A. W. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20972856 · Cited by 112 · see citing works
Shah, T., Leurgans, S. E., Mehta, R. I., Yang, J., Galloway, C. A., Bentley, K. L. D. M., Schneider, J. A., & Mehta, R. I. (2022) · The Journal of Experimental Medicine · doi:10.1084/jem.20220618 · Cited by 108 · see citing works
Self-citationThe Glymphatic System: A Novel Therapeutic Target for Stroke Treatment
Lv, T., Zhao, B., Hu, Q., & Zhang, X. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.689098 · Cited by 105 · see citing works
Kaur, J., Fahmy, L. M., Davoodi‐Bojd, E., Zhang, L., Ding, G., Hu, J., Zhang, Z., Chopp, M., & Jiang, Q. (2021) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2021.665803 · Cited by 104 · see citing works
The glymphatic system and meningeal lymphatics of the brain: new understanding of brain clearance
Yankova, G., Bogomyakova, O. B., & Тулупов, А. А. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0106 · Cited by 104 · see citing works
Neurofluid Dynamics and the Glymphatic System: A Neuroimaging Perspective
Taoka, T., & Naganawa, S. (2020) · Korean Journal of Radiology · doi:10.3348/kjr.2020.0042 · Cited by 97 · see citing works
A clinical primer for the glymphatic system
Carlstrom, L. P., Eltanahy, A. M., Perry, A., Rabinstein, A. A., Elder, B. D., Morris, J. M., Meyer, F. B., Graffeo, C. S., Lundgaard, I., & Burns, T. C. (2021) · Brain · doi:10.1093/brain/awab428 · Cited by 100 · see citing works
Li, G., Cao, Y., Tang, X., Huang, J., Cai, L., & Zhou, L. (2022) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x221098145 · Cited by 99 · see citing works
Mestre, H., Verma, N., Greene, T. D., Lin, L. A., Ladrón-de-Guevara, A., Sweeney, A. M., Liu, G., Thomas, V. K., Galloway, C. A., Bentley, K. L. D. M., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31257-9 · Cited by 94 · see citing works
Self-citationThe role of brain perivascular space burden in early-stage Parkinson’s disease
Shen, T., Yue, Y., Zhao, S., Xie, J., Chen, Y., Tian, J., Lv, W., Lo, C. Z., Hsu, Y., Kober, T., et al. (2021) · npj Parkinson s Disease · doi:10.1038/s41531-021-00155-0 · Cited by 91 · see citing works
Taoka, T., & Naganawa, S. (2020) · Japanese Journal of Radiology · doi:10.1007/s11604-020-01017-0 · Cited by 88 · see citing works
Troili, F., Cipollini, V., Moci, M., Morena, E., Palotai, M., Rinaldi, V., Romano, C., Ristori, G., Giubilei, F., Salvetti, M., et al. (2020) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2020.00017 · Cited by 91 · see citing works
Mehta, R. I., & Schneider, J. A. (2021) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000912 · Cited by 84 · see citing works
Self-citationZhang, Y., Zhang, R., Ye, Y., Wang, S., Jiaerken, Y., Hong, H., Li, K., Zeng, Q., Luo, X., Xu, X., et al. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.693787 · Cited by 84 · see citing works
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 84 · see citing works
Glymphatic System Pathology and Neuroinflammation as Two Risk Factors of Neurodegeneration
Szlufik, S., Kopeć, K., Szleszkowski, S., & Koziorowski, D. (2024) · Cells · doi:10.3390/cells13030286 · Cited by 81 · see citing works
Xue, Y., Liu, N., Zhang, M., Ren, X., Tang, J., & Fu, J. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.04.008 · Cited by 71 · see citing works
Dysfunction of the Glymphatic System Might Be Related to Iron Deposition in the Normal Aging Brain
Zhou, W., Shen, B., Shen, W., Chen, H., Zheng, Y.-F., & Fei, J.-J. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.559603 · Cited by 75 · see citing works
The effect of aquaporin-4 mis-localization on Aβ deposition in mice
Pedersen, T. J., Keil, S. A., Han, W., Wang, M. X., & Iliff, J. J. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106100 · Cited by 73 · see citing works
Fluid Flow and Mass Transport in Brain Tissue
Ray, L., & Heys, J. J. (2019) · Fluids · doi:10.3390/fluids4040196 · Cited by 75 · see citing works
Stevens, K. A., Cai, S., Ladrón-de-Guevara, A., Sun, J., Zheng, X., Du, T., Thomas, J. H., Nedergaard, M., Karniadakis, G. E., & Kelley, D. H. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2217744120 · Cited by 74 · see citing works
Self-citationNoninvasive Magnetic Resonance Imaging Measures of Glymphatic System Activity
Kamagata, K., Saito, Y., Andica, C., Uchida, W., Takabayashi, K., Yoshida, S., Hagiwara, A., Fujita, S., Nakaya, M., Akashi, T., et al. (2023) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.28977 · Cited by 76 · see citing works
VanElzakker, M. B., Bues, H. F., Brusaferri, L., Kim, M., Saadi, D., Ratai, E., Dougherty, D. D., & Loggia, M. L. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.04.015 · Cited by 73 · see citing works
Coupland, K., Lendahl, U., & Karlström, H. (2018) · Stroke · doi:10.1161/strokeaha.118.021560 · Cited by 74 · see citing works
Zhang, R., Huang, P., Jiaerken, Y., Wang, S., Hong, H., Luo, X., Xu, X., Yu, X., Li, K., Zeng, Q., et al. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20904840 · Cited by 72 · see citing works
Intracranial pulsatility in patients with cerebral small vessel disease: a systematic review
Shi, Y., Thrippleton, M. J., Marshall, I., & Wardlaw, J. M. (2017) · Clinical Science · doi:10.1042/cs20171280 · Cited by 69 · see citing works
Glymphatic System and Psychiatric Disorders: A Rapid Comprehensive Scoping Review
Barlattani, T., Grandinetti, P., Cintio, A. D., Montemagno, A., Testa, R., D’Amelio, C., Olivieri, L., Tomasetti, C., Rossi, A., Pacitti, F., et al. (2024) · Current Neuropharmacology · doi:10.2174/1570159x22666240130091235 · Cited by 69 · see citing works
Meng, J., Shen, M.-Q., Lu, Y., Feng, H., Chen, X., Xu, D.-Q., Wu, G.-H., Cheng, Q., Wang, L., & Gui, Q. (2023) · Journal of Neurology · doi:10.1007/s00415-023-12004-6 · Cited by 66 · see citing works
Cardiac and respiration-induced brain deformations in humans quantified with high-field MRI
Sloots, J. J., Biessels, G. J., & Zwanenburg, J. J. M. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.116581 · Cited by 66 · see citing works
Licastro, E., Pignataro, G., Iliff, J. J., Xiang, Y., Lo, E. H., Hayakawa, K., & Esposito, E. (2024) · Communications Biology · doi:10.1038/s42003-024-05911-5 · Cited by 69 · see citing works
Spectral Diffusion Analysis of Intravoxel Incoherent Motion MRI in Cerebral Small Vessel Disease
Wong, S. M., Backes, W. H., Drenthen, G. S., Zhang, C. E., Voorter, P., Staals, J., van Oostenbrugge, R. J., & Jansen, J. F. A. (2019) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.26920 · Cited by 62 · see citing works
Rivera‐Rivera, L. A., Cody, K. A., Eisenmenger, L. B., Cary, P., Rowley, H. A., Carlsson, C. M., Johnson, S. C., & Johnson, K. M. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20910302 · Cited by 62 · see citing works
Hagemann, T. L., Powers, B. E., Lin, N., Mohamed, A. F., Dague, K. L., Hannah, S. C., Bachmann, G., Mazur, C., Rigo, F., Olsen, A. L., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abg4711 · Cited by 62 · see citing works
Neuroprotective Strategies in Aneurysmal Subarachnoid Hemorrhage (aSAH)
Weiland, J., Beez, A., Westermaier, T., Kunze, E., Sirén, A., & Lilla, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115442 · Cited by 60 · see citing works
Cerebral white matter vasculature: still uncharted?
Smirnov, M., Destrieux, C., & Maldonado, I. L. (2021) · Brain · doi:10.1093/brain/awab273 · Cited by 59 · see citing works
Air pollution, glymphatic impairment, and Alzheimer's disease
Hussain, R., Graham, U. M., Elder, A. C. P., & Nedergaard, M. (2023) · Trends in Neurosciences · doi:10.1016/j.tins.2023.08.010 · Cited by 60 · see citing works
Self-citationSemyachkina-Glushkovskaya, O. V., Postnov, D. E., Penzel, T., & Kurths, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176293 · Cited by 60 · see citing works
Semyachkina-Glushkovskaya, O. V., Penzel, T., Андреевна, Б. И., Khorovodov, A. P., Fedosov, I. V., Yu, T., Karandin, G., Evsukova, A., Elovenko, D., Adushkina, V., et al. (2021) · Cells · doi:10.3390/cells10123289 · Cited by 59 · see citing works
Physiology of Glymphatic Solute Transport and Waste Clearance from the Brain
Zhao, L., Tannenbaum, A., Bakker, E. N. T. P., & Benveniste, H. (2022) · Physiology · doi:10.1152/physiol.00015.2022 · Cited by 61 · see citing works
Romay, M. C., Knutsen, R. H., Ma, F., Mompeón, A., Hernandez, G. E., Salvador, J., Mirkov, S., Batra, A., Sullivan, D. P., Procissi, D., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci166134 · Cited by 60 · see citing works
Relationship of Perivascular Space Markers With Incident Dementia in Cerebral Small Vessel Disease
Hong, H., Tozer, D. J., & Markus, H. S. (2024) · Stroke · doi:10.1161/strokeaha.123.045857 · Cited by 56 · see citing works
Henderson, A. R., Choi, H., & Lee, E. (2020) · Micromachines · doi:10.3390/mi11020147 · Cited by 54 · see citing works
Glymphatic System Dysfunction: A Novel Mediator of Sleep Disorders and Headaches
Yi, T., Gao, P., Zhu, T., Yin, H., & Jin, S. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.885020 · Cited by 57 · see citing works
The glymphatic system and its role in cerebral homeostasis
Benveniste, H., Elkin, R., Heerdt, P. M., Koundal, S., Xue, Y., Lee, H., Wardlaw, J. M., & Tannenbaum, A. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00852.2019 · Cited by 54 · see citing works
Neurovascular-glymphatic dysfunction and white matter lesions
Sabayan, B., & Westendorp, R. G. J. (2021) · GeroScience · doi:10.1007/s11357-021-00361-x · Cited by 54 · see citing works
Stroke and the neurovascular unit: glial cells, sex differences, and hypertension
Morrison, H. W., & Filosa, J. A. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00333.2018 · Cited by 54 · see citing works
The glymphatic system and cerebral small vessel disease
Ang, P. S., Zhang, D. M., Azizi, S., de Matos, S. N., & Brorson, J. R. (2024) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2024.107557 · Cited by 56 · see citing works
van Osch, M. J. P., Wåhlin, A., Scheyhing, P., Mossige, I., Hirschler, L., Eklund, A., Mogensen, K., Gomolka, R. S., Radbruch, A., Qvarlander, S., et al. (2024) · NMR in Biomedicine · doi:10.1002/nbm.5159 · Cited by 55 · see citing works
Self-citationKe, Z., Mo, Y., Li, J., Yang, D., Huang, L., Yang, Z., Qin, R., Mao, C., Lv, W., Huang, Y., et al. (2022) · Brain Sciences · doi:10.3390/brainsci12121611 · Cited by 51 · see citing works
Perivascular space dysfunction in cerebral small vessel disease is related to neuroinflammation
Hong, H., Tozer, D. J., Chen, Y., Brown, R. B., Low, A., & Markus, H. S. (2024) · Brain · doi:10.1093/brain/awae357 · Cited by 47 · see citing works
Si, X., Gu, L., Song, Z., Zhou, C., Fang, Y., Jin, C., Wu, J., Gao, T., Guo, T., Guan, X., et al. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.580853 · Cited by 46 · see citing works
Li, Y., Zhu, Z., Chen, J., Zhang, M., Yang, Y., & Huang, P. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00161 · Cited by 45 · see citing works
Neuropathology of the Common Forms of Dementia
Mehta, R. I., & Schneider, J. A. (2022) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2022.07.005 · Cited by 44 · see citing works
Self-citationLiu, E., Sun, L., Zhang, Y., Wang, A., & Yan, J. (2019) · Acta neurochirurgica. Supplementum · doi:10.1007/978-3-030-04615-6_10 · Cited by 44 · see citing works
Zhang, M., Tang, J., Xia, D., Yang, X., Ren, X., Huang, Q., Shi, L., Tang, W., & Fu, J. (2023) · European Radiology · doi:10.1007/s00330-023-09796-6 · Cited by 43 · see citing works
Potential Role of Venular Amyloid in Alzheimer’s Disease Pathogenesis
Morrone, C. D., Bishay, J., & McLaurin, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21061985 · Cited by 41 · see citing works
Perivascular pumping of cerebrospinal fluid in the brain with a valve mechanism
Gan, Y., von Holstein‐Rathlou, S., Nedergaard, M., Stevens, K. A., Thomas, J. H., & Kelley, D. H. (2023) · Journal of The Royal Society Interface · doi:10.1098/rsif.2023.0288 · Cited by 41 · see citing works
Self-citationLiu, H., Yang, S., He, W., Liu, X., Sun, S., Wang, S., Wang, Y., Zhou, X., Tang, T., Xia, J., et al. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2021.789918 · Cited by 41 · see citing works
Automated Methods for Detecting and Quantitation of Enlarged Perivascular spaces on MRI
Moses, J., Sinclair, B., Law, M., O'Brien, T. J., & Vivash, L. E. (2022) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.28369 · Cited by 41 · see citing works
Clearance Systems in the Brain, From Structure to Function
Liu, J., Guo, Y., Zhang, C., Zeng, Y., Luo, Y., & Wang, G. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.729706 · Cited by 41 · see citing works
High dilated perivascular space burden: a new MRI marker for risk of intracerebral hemorrhage
Duperron, M., Tzourio, C., Schilling, S., Zhu, Y., Soumaré, A., Mazoyer, B. M., & Debette, S. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.08.031 · Cited by 41 · see citing works
Molecular mechanisms of cognitive impairment associated with stroke
Kaur, M., & Sharma, S. (2022) · Metabolic Brain Disease · doi:10.1007/s11011-022-00901-0 · Cited by 42 · see citing works
The lymphatic system: a therapeutic target for central nervous system disorders
Lü, H., Cao, Y., Hu, J., Xu, J., Liu, Q., Huang, S., & Duan, C. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.355741 · Cited by 39 · see citing works
Magnetic Resonance Imaging and Modeling of the Glymphatic System
Kaur, J., Davoodi‐Bojd, E., Fahmy, L. M., Zhang, L., Ding, G., Hu, J., Zhang, Z., Chopp, M., & Jiang, Q. (2020) · Diagnostics · doi:10.3390/diagnostics10060344 · Cited by 40 · see citing works
Glymphatic System Dysfunction in Central Nervous System Diseases and Mood Disorders
Zhang, D., Li, X., & Li, B. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.873697 · Cited by 40 · see citing works
van den Kerkhof, M., van der Thiel, M. M., van Oostenbrugge, R. J., Postma, A. A., Kroon, A. A., Backes, W. H., & Jansen, J. F. A. (2023) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x231153374 · Cited by 37 · see citing works
- Authors
- Mestre, H., Kostrikov, S., Mehta, R. I., & Nedergaard, M.
- Affiliations
- University of Rochester Medicine (US)
- University of Copenhagen (DK)
- Corresponding author
- Nedergaard, Maiken
- Venue
- Clinical Science
- Publisher
- Portland Press Ltd.
- Published
- 2017-08-10
- Volume
- 131
- Issue
- 17
- Pages
- 2257-2274
- ISSN
- 0143-5221 (ISSN-L)
- 1470-8736
- PMC
- PMC5567781
- OpenAlex
- W2742497781
- Cited by
- 403
- References
- 127
- Citations by year
- 2026: 54 · 2025: 58 · 2024: 66 · 2023: 52 · 2022: 53 · 2021: 40 · 2020: 32 · 2019: 32 · 2018: 14 · 2017: 2
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Clinical Science (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Funders
- Lundbeckfonden (R155-2016–552)
- Israel Science Foundation
- Novo Nordisk Fonden (NNF13OC0004258)
- National Institute on Aging (R01AG048769)
- National Institute of Neurological Disorders and Stroke (R01NS078304, K08NS089830, R01NS100366)
- 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
- cerebral small vessel disease, enlarged perivascular spaces, glymphatic system, glymphatic dysfunction, aquaporin-4, perivascular spaces, therapeutic target
- MeSH terms
- Animals, Blood Vessels, Brain, Humans, Aquaporin 4, Cerebral Small Vessel Diseases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
