Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system.
Open accessAbstract
The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity.
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?
Disruption of glymphatic function results in lower levels of TBI-associated biomarkers in the cervical lymph nodes and bloodstream.
“disruption of glymphatic function results in lower levels of TBI-associated biomarkers in the cervical lymph nodes and bloodstream”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Plog et al., 2015
The brain glymphatic and meningeal lymphatic systems work together to clear waste and macromolecules from the brain parenchyma in homeostasis and following injury.
“The brain glymphatic and meningeal lymphatic systems work together to clear waste and macromolecules from the brain parenchyma in homeostasis and following injury”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Plog et al., 2015
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-citationSleep 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-citationNational Center for Injury Prevention and Control (U.S.). Division of Injury Response., Faul, M., Wald, M. M., Wu, L., & Coronado, V. G. (2010) · doi:10.15620/cdc.5571 · Cited by 3,494 · see citing works
Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition
Carney, N., Totten, A., O'Reilly, C., Ullman, J., Hawryluk, G., Bell, M., Bratton, S., Chesnut, R., Harris, O., Kissoon, N., et al. (2016) · Neurosurgery · doi:10.1227/neu.0000000000001432 · Cited by 3,403 · see citing works
Development, maintenance and disruption of the blood-brain barrier
Obermeier, B., Daneman, R., & Ransohoff, R. M. (2013) · Nature Medicine · doi:10.1038/nm.3407 · Cited by 2,452 · see citing works
Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke
Manley, G. T., Fujimura, M., Ma, T., Noshita, N., Filiz, F., Bollen, A. W., Chan, P. H., & Verkman, A. S. (2000) · Nature Medicine · doi:10.1038/72256 · Cited by 1,501 · see citing works
Kaipainen, A., Korhonen, J., Mustonen, T., van Hinsbergh, V. W. M., Fang, G. H., Dumont, D., Breitman, M. L., & Alitalo, K. K. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.8.3566 · Cited by 1,420 · see citing works
Animal models of traumatic brain injury
Xiong, Y., Mahmood, A., & Chopp, M. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3407 · Cited by 1,413 · see citing works
Changing patterns in the epidemiology of traumatic brain injury
Roozenbeek, B., Maas, A. I. R., & Menon, D. K. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.22 · Cited by 1,368 · 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-citationSynaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo
Cirrito, J. R., Yamada, K. A., Finn, M. B., Sloviter, R. S., Bales, K. R., May, P. C., Schoepp, D. D., Paul, S. M., Mennerick, S., & Holtzman, D. M. (2005) · Neuron · doi:10.1016/j.neuron.2005.10.028 · Cited by 1,265 · see citing works
A systematic review of brain injury epidemiology in Europe
Tagliaferri, F., Compagnone, C., Koršič, M., Servadei, F., & Kraus, J. F. (2005) · Acta Neurochirurgica · doi:10.1007/s00701-005-0651-y · Cited by 1,223 · 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-citationBrain oedema in focal ischaemia: molecular pathophysiology and theoretical implications
Simard, J. M., Kent, T. A., Chen, M., Tarasov, K. V., & Gerzanich, V. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70055-8 · Cited by 799 · 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
Self-citationAquaporin‐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
Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease
Brenner, M., Johnson, T., Boespflug‐Tanguy, O., Rodriguez, D., Goldman, J. E., & Messing, A. (2001) · Nature Genetics · doi:10.1038/83679 · Cited by 689 · see citing works
Blood–Brain Barrier Pathophysiology in Traumatic Brain Injury
Chodobski, A., Zink, B. J., & Szmydynger‐Chodobska, J. (2011) · Translational Stroke Research · doi:10.1007/s12975-011-0125-x · Cited by 655 · see citing works
Thorne, R. G., & Nicholson, C. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509425103 · Cited by 641 · see citing works
The neurobiology of glia in the context of water and ion homeostasis
Simard, M. F., & Nedergaard, M. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.09.053 · Cited by 607 · see citing works
Self-citationBiomarkers of mild traumatic brain injury in cerebrospinal fluid and blood
Zetterberg, H., Smith, D. H., & Blennow, K. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.9 · Cited by 601 · see citing works
Johnston, 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
Papadopoulos, M. C., & Verkman, A. S. (2007) · Pediatric Nephrology · doi:10.1007/s00467-006-0411-0 · Cited by 455 · see citing works
Cserr, H. F., Harling‐Berg, C. J., & Knopf, P. M. (1992) · Brain Pathology · doi:10.1111/j.1750-3639.1992.tb00703.x · Cited by 450 · see citing works
Do women fare worse: a metaanalysis of gender differences in traumatic brain injury outcome
Farace, E., & Alves, W. M. (2000) · Journal of neurosurgery · doi:10.3171/jns.2000.93.4.0539 · Cited by 446 · see citing works
Diaz-Arrastia, R., Wang, K. K. W., Papa, L., Sorani, M. D., Yue, J. K., Puccio, A., McMahon, P., Inoue, T., Yuh, E., Lingsma, H. F., et al. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2013.3040 · Cited by 434 · see citing works
VI. Indications for Intracranial Pressure Monitoring
Bratton, S. L., Chestnut, R. M., Ghajar, J., et al. (2007) · Journal of Neurotrauma · doi:10.1089/neu.2007.9990 · Cited by 406 · see citing works
Cytotoxic edema: mechanisms of pathological cell swelling
Liang, D., Bhatta, S., Gerzanich, V., & Simard, J. M. (2007) · Neurosurgical FOCUS · doi:10.3171/foc.2007.22.5.3 · Cited by 399 · see citing works
Yamada, K., Cirrito, J. R., Stewart, F. R., Jiang, H., Finn, M. B., Holmes, B. B., Binder, L. I., Mandelkow, E.-M., Diamond, M. I., Lee, V. M.-Y., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2569-11.2011 · Cited by 351 · see citing works
Hemorrhagic Progression of a Contusion after Traumatic Brain Injury: A Review
Kurland, D. B., Hong, C. M., Aarabi, B., Gerzanich, V., & Simard, J. M. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2011.2122 · Cited by 349 · 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
A review of progress in understanding the pathophysiology and treatment of brain edema
Marmarou, A. (2007) · Neurosurgical FOCUS · doi:10.3171/foc.2007.22.5.2 · Cited by 333 · see citing works
Ren, 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-citationAquaporin-4 Gene Disruption in Mice Reduces Brain Swelling and Mortality in Pneumococcal Meningitis
Papadopoulos, M. C., & Verkman, A. S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413627200 · Cited by 301 · see citing works
Care of War Veterans with Mild Traumatic Brain Injury — Flawed Perspectives
Hoge, C. W., Goldberg, H. M., & Castro, C. A. (2009) · New England Journal of Medicine · doi:10.1056/nejmp0810606 · Cited by 264 · see citing works
Thrane, A. S., Rappold, P. M., Fujita, T., Torres, A., Bekar, L. K., Takano, T., Peng, W., Wang, F., Rangroo Thrane, V., Enger, R., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015217108 · Cited by 254 · see citing works
Self-citationAmiry-Moghaddam, M. R., Xue, R., Haug, F. Š., Neely, J. D., Bhardwaj, A., Agre, P. C., Adams, M. E., Froehner, S. C., Mori, S., & Ottersen, O. P. (2004) · The FASEB Journal · doi:10.1096/fj.03-0869fje · Cited by 241 · see citing works
Manaenko, A., Chen, H., Kammer, J., Zhang, J. H., & Tang, J. (2010) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2010.12.013 · Cited by 233 · see citing works
Bulk flow of interstitial fluid after intracranial injection of Blue Dextran 2000
Cserr, H. F., & Ostrach, L. H. (1974) · Experimental Neurology · doi:10.1016/0014-4886(74)90099-5 · Cited by 224 · see citing works
Biomarkers for the Diagnosis and Prognosis of Mild Traumatic Brain Injury/Concussion
Jeter, C. B., Hergenroeder, G. W., Hylin, M. J., Redell, J. B., Moore, A. N., & Dash, P. K. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2012.2439 · Cited by 223 · see citing works
Indications for Intracranial Pressure Monitoring
(2000) · Journal of Neurotrauma · doi:10.1089/neu.2000.17.479 · Cited by 218 · 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-citationBradbury, M. W. B., & Westrop, R. J. (1983) · The Journal of Physiology · doi:10.1113/jphysiol.1983.sp014731 · Cited by 211 · see citing works
Sulfonylurea Receptor 1 in Central Nervous System Injury: A Focused Review
Simard, J. M., Woo, S. K., Schwartzbauer, G., & Gerzanich, V. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.91 · Cited by 201 · see citing works
In VivoMeasurement of Brain Extracellular Space Diffusion by Cortical Surface Photobleaching
Binder, D. K., Papadopoulos, M. C., Haggie, P. M., & Verkman, A. S. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2294-04.2004 · Cited by 192 · see citing works
Blood-based diagnostics of traumatic brain injuries
Mondello, S., Muller, U., Jeromin, A., Streeter, J., Hayes, R., & Wang, K. K. W. (2011) · Expert Review of Molecular Diagnostics · doi:10.1586/erm.10.104 · Cited by 181 · see citing works
Kövesdi, E., Lückl, J., Bukovics, P., Farkas, O., Pál, J., Czeiter, E., Szellár, D., Doczi, T. P., Komoly, S., & Büki, A. (2009) · Acta Neurochirurgica · doi:10.1007/s00701-009-0463-6 · Cited by 172 · see citing works
Vascular endothelial growth factor receptor 3 directly regulates murine neurogenesisPreprint
Calvo, C.-F., Fontaine, R. H., Soueid, J., Tammela, T., Makinen, T., Alfaro-Cervello, C., Bonnaud, F., Miguez, A., Benhaim, L., Xu, Y., et al. (2011) · Genes & Development · doi:10.1101/gad.615311 · Cited by 169 · see citing works
Clinical correlates in an experimental model of repetitive mild brain injury
Mannix, R., Meehan, W. P., III, Mandeville, J. B., Grant, P. E., Gray, T., Berglass, J., Zhang, J., Bryant, J., Rezaie, S., Chung, J. Y., et al. (2013) · Annals of Neurology · doi:10.1002/ana.23858 · Cited by 158 · see citing works
Simard, J. M., Kahle, K. T., & Gerzanich, V. (2009) · Journal of neurosurgery · doi:10.3171/2009.11.jns081052 · Cited by 146 · see citing works
Isoflurane exerts neuroprotective actions at or near the time of severe traumatic brain injury
Statler, K. D., Alexander, H. L., Vagni, V., Holubkov, R., Dixon, C. E., Clark, R. S. B., Jenkins, L. W., & Kochanek, P. M. (2006) · Brain Research · doi:10.1016/j.brainres.2005.12.106 · Cited by 140 · see citing works
Systematic Review of Clinical Research on Biomarkers for Pediatric Traumatic Brain Injury
Papa, L., Ramia, M. M., Kelly, J. M., Burks, S. S., Pawlowicz, A., & Berger, R. P. (2012) · Journal of Neurotrauma · doi:10.1089/neu.2012.2545 · Cited by 136 · see citing works
In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis
Ulrich, J. D., Burchett, J. M., Restivo, J. L., Schuler, D. R., Verghese, P. B., Mahan, T. E., Landreth, G. E., Castellano, J. M., Jiang, H., Cirrito, J. R., et al. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-13 · Cited by 128 · see citing works
Murtha, L. A., Yang, Q., Parsons, M. W., Levi, C. R., Beard, D. J., Spratt, N. J., & McLeod, D. D. (2014) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-11-12 · Cited by 124 · see citing works
Langlois, J. A., & Sattin, R. W. (2005) · Journal of Head Trauma Rehabilitation · doi:10.1097/00001199-200505000-00001 · Cited by 122 · 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
Cerebrospinal Fluid Transport: a Lymphatic Perspective
Johnston, M., & Papaiconomou, C. (2002) · Physiology · doi:10.1152/nips.01400.2002 · Cited by 110 · see citing works
Biomarker-based dissection of neurodegenerative diseases
Olsson, B., Zetterberg, H., Hampel, H. J., & Blennow, K. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.04.006 · Cited by 96 · see citing works
Katada, R., Akdemir, G., Asavapanumas, N., Ratelade, J., Zhang, H., & Verkman, A. S. (2013) · The FASEB Journal · doi:10.1096/fj.13-231274 · Cited by 80 · see citing works
Novel microdialysis method to assess neuropeptides and large molecules in free-moving mouse
Takeda, S., Sato, N., Ikimura, K., Nishino, H., Rakugi, H., & Morishita, R. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.04.035 · Cited by 63 · see citing works
Akdemir, G., Ratelade, J., Asavapanumas, N., & Verkman, A. S. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.03.073 · Cited by 61 · see citing works
The pathophysiology of brain edema and elevated intracranial pressure.
Marmarou, A. (2004) · Cleveland Clinic Journal of Medicine · doi:10.3949/ccjm.71.suppl_1.s6 · Cited by 54 · see citing works
Mild traumatic brain injury (MTBI) leads to spatial learning deficits
Darwish, H., Mahmood, A., Schallert, T. J., Chopp, M., & Therrien, B. A. (2012) · Brain Injury · doi:10.3109/02699052.2011.635362 · Cited by 52 · see citing works
Effect of AlCl3 and other acids on cerebrospinal fluid production: a correction.
VOGH, B. P., GODMAN, D. R., & Maren, T. H. (1987) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)39243-8 · Cited by 40 · see citing works
Hourly neurologic assessments for traumatic brain injury in the ICU
Stone, J. J., Childs, S. M., Smith, L. E., et al. (2013) · Neurological Research · doi:10.1179/1743132813y.0000000285 · Cited by 32 · see citing works
Endoscopic Endonasal Cavernous Sinus Surgery: An Anatomic Study
Jho, H., & Alfieri, A. (2001) · Neurosurgery · doi:10.1097/00006123-200111000-00057 · Cited by 25 · see citing works
Amtorp, O. (1979) · The Journal of Physiology · doi:10.1113/jphysiol.1979.sp012916 · Cited by 21 · see citing works
Changing paradigms for the treatment of brain metastasis
Sheehan, J. P., & Sheehan, J. M. (2007) · Neurosurgical FOCUS · doi:10.3171/foc.2007.22.3.1 · Cited by 19 · see citing works
High Serum S100B Levels for Trauma Patients without Head Injuries
Herrmann, M. (2001) · Neurosurgery · doi:10.1097/00006123-200111000-00058 · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease
Iadecola, C. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.030 · Cited by 2,480 · see citing works
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-citationClearance systems in the brain—implications for Alzheimer disease
Tarasoff-Conway, J. M., Carare, R. O., Osorio, R. S., Glodzik, L., Butler, T., Fieremans, E., Axel, L., Rusinek, H., Nicholson, C., Zlokovic, B. V., et al. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.119 · Cited by 1,678 · see citing works
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-citationThe far-reaching scope of neuroinflammation after traumatic brain injury
Simon, D. W., McGeachy, M. J., Bayır, H., Clark, R. S. B., Loane, D. J., & Kochanek, P. M. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.13 · Cited by 1,190 · see citing works
Glial fibrillary acidic protein: From intermediate filament assembly and gliosis to neurobiomarker
Yang, Z., & Wang, K. K. W. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.04.003 · Cited by 1,050 · see citing works
Neuroimmunology of Traumatic Brain Injury: Time for a Paradigm Shift
Jassam, Y. N., Izzy, S., Whalen, M., McGavern, D. B., & El Khoury, J. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.010 · Cited by 799 · see citing works
Aquaporin-4-dependent glymphatic solute transport in the rodent brain
Mestre, H., Hablitz, L. M., Xavier, A. L., Feng, W., Zou, W., Pu, T., Monai, H., Murlidharan, G., Castellanos Rivera, R. M., Simon, M. J., et al. (2018) · eLife · doi:10.7554/elife.40070 · Cited by 738 · see citing works
Self-citationGlymphatic MRI in idiopathic normal pressure hydrocephalus
Ringstad, G., Vatnehol, S. A. S., & Eide, P. K. (2017) · Brain · doi:10.1093/brain/awx191 · Cited by 722 · see citing works
Revisiting the Mechanisms of CNS Immune Privilege
Louveau, A., Harris, T. H., & Kipnis, J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.006 · Cited by 682 · see citing works
The Brain’s Glymphatic System: Current Controversies
Mestre, H., Mori, Y., & Nedergaard, M. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.04.003 · Cited by 609 · see citing works
Self-citationSuppression 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-citationThe Glymphatic System and Waste Clearance with Brain Aging: A Review
Benveniste, H., Liu, X., Koundal, S., Sanggaard, S., Lee, H., & Wardlaw, J. (2019) · Gerontology · doi:10.1159/000490349 · Cited by 517 · see citing works
Perivascular spaces, glymphatic dysfunction, and small vessel disease
Mestre, H., Kostrikov, S., Mehta, R. I., & Nedergaard, M. (2017) · Clinical Science · doi:10.1042/cs20160381 · Cited by 403 · see citing works
Self-citationMeningeal lymphatic dysfunction exacerbates traumatic brain injury pathogenesis.
Bolte, A. C., Dutta, A. B., Hurt, M. E., Smirnov, I., Kovacs, M. A., McKee, C. A., Ennerfelt, H. E., Shapiro, D., Nguyen, B. H., Frost, E. L., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18113-4 · Cited by 357 · see citing works
Alves de Lima, K., Rustenhoven, J., & Kipnis, J. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-102319-103410 · Cited by 348 · 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-citationImpaired Glymphatic Transport in Spontaneously Hypertensive Rats
Mortensen, K. N., Sanggaard, S., Mestre, H., Lee, H., Kostrikov, S., Xavier, A. L. R., Gjedde, A., Benveniste, H., & Nedergaard, M. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.1974-18.2019 · Cited by 266 · see citing works
Self-citationSleep-Wake Disturbances After Traumatic Brain Injury: Synthesis of Human and Animal Studies
Sandsmark, D. K., Elliott, J. E., & Lim, M. M. (2017) · Sleep · doi:10.1093/sleep/zsx044 · Cited by 183 · see citing works
Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease
Derk, J., Jones, H. E., Como, C., Pawlikowski, B., & Siegenthaler, J. A. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.703944 · Cited by 120 · 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
New astroglial injury-defined biomarkers for neurotrauma assessment
Halford, J., Shen, S., Itamura, K., Levine, J., Chong, A. C., Czerwieniec, G., Glenn, T. C., Hovda, D. A., Vespa, P., Bullock, R., et al. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17724681 · Cited by 75 · see citing works
Bazarian, J. J., Zetterberg, H., Buki, A., Dengler, B. A., Diaz-Arrastia, R., Korley, F. K., Lazarus, R., Meier, T. B., Mondello, S., Moritz, K., et al. (2025) · Journal of Neurotrauma · doi:10.1089/neu.2024.0581 · Cited by 61 · see citing works
- Authors
- Plog, B. A., Dashnaw, M. L., Hitomi, E., Peng, W., Liao, Y., Lou, N., Deane, R., & Nedergaard, M.
- Affiliations
- University of Rochester Medicine (US)
- Corresponding author
- Nedergaard, Maiken
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-01-14
- Volume
- 35
- Issue
- 2
- Pages
- 518-526
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4293408
- OpenAlex
- W2032220418
- Cited by
- 525
- References
- 70
- Citations by year
- 2026: 46 · 2025: 41 · 2024: 47 · 2023: 43 · 2022: 57 · 2021: 47 · 2020: 46 · 2019: 40 · 2018: 54 · 2017: 38 · 2016: 33 · 2015: 32
- FWCI
- 36.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- National Institutes of Health
- National Institute on Aging (R01AG048769)
- National Institute of Neurological Disorders and Stroke (R01NS078304, R01NS078167, R01NS075177)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD076892)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- traumatic brain injury, blood-based biomarkers, glymphatic system, cerebrospinal fluid, S100β, glial fibrillary acidic protein, neuron-specific enolase, sleep deprivation, serum biomarkers
- MeSH terms
- Animals, Blood-Brain Barrier, Brain Injuries, Female, Glial Fibrillary Acidic Protein, Metabolic Clearance Rate, Mice, Inbred C57BL, Neuroglia, Sleep Deprivation, Biomarkers, Extracellular Fluid, Mice, S100 Calcium Binding Protein beta Subunit
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