Meningeal lymphatics clear erythrocytes that arise from subarachnoid hemorrhage.
Open accessAbstract
Extravasated erythrocytes in cerebrospinal fluid (CSF) critically contribute to the pathogenesis of subarachnoid hemorrhage (SAH). Meningeal lymphatics have been reported to drain macromolecules and immune cells from CSF into cervical lymph nodes (CLNs). However, whether meningeal lymphatics are involved in clearing extravasated erythrocytes in CSF after SAH remains unclear. Here we show that a markedly higher number of erythrocytes are accumulated in the lymphatics of CLNs and meningeal lymphatics after SAH. When the meningeal lymphatics are depleted in a mouse model of SAH, the degree of erythrocyte aggregation in CLNs is significantly lower, while the associated neuroinflammation and the neurologic deficits are dramatically exacerbated. In addition, during SAH lymph flow is increased but without significant lymphangiogenesis and lymphangiectasia. Taken together, this work demonstrates that the meningeal lymphatics drain extravasated erythrocytes from CSF into CLNs after SAH, while suggesting that modulating this draining may offer therapeutic approaches to alleviate SAH severity.
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In a subarachnoid hemorrhage model, erythrocytes accrue in the cervical lymph nodes via meningeal lymphatics following injury, and ablation of meningeal lymphatic vessels leads to less erythrocyte aggregation and greater neuroinflammation and neurological defects.
“erythrocytes accrue in the cervical lymph nodes via meningeal lymphatics following injury, and ablation of meningeal lymphatic vessels leads to less erythrocyte aggregation and greater neuroinflammation and neurological defects”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Chen et al., 2020
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Structural 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
Johnson, C. O., Nguyen, M., Roth, G. A., Nichols, E. L., Alam, S., Abate, D., Abd-Allah, F., Abdelalim, A., Abraha, H. N., Abu-Rmeileh, N. M., et al. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30034-1 · Cited by 3,324 · see citing works
Feigin, V. L., Lawes, C. M., Bennett, D. A., Barker-Collo, S. L., & Parag, V. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70025-0 · Cited by 2,855 · 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
van Gijn, J., Kerr, R. S. C., & Rinkel, G. J. E. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60153-6 · Cited by 1,703 · see citing works
Functional aspects of meningeal lymphatics in ageing and Alzheimer’s disease
Da Mesquita, S., Louveau, A., Vaccari, A., Smirnov, I., Cornelison, R. C., Kingsmore, K. M., Contarino, C., Onengut-Gumuscu, S., Farber, E., Raper, D., et al. (2018) · Nature · doi:10.1038/s41586-018-0368-8 · Cited by 1,445 · see citing works
CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature.
Louveau, A., Herz, J., Alme, M. N., Salvador, A. F., Dong, M. Q., Viar, K. E., Herod, S. G., Knopp, J., Setliff, J. C., Lupi, A. L., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0227-9 · Cited by 956 · see citing works
Ma, Q., Ineichen, B. V., Detmar, M., & Proulx, S. T. (2017) · Nature Communications · doi:10.1038/s41467-017-01484-6 · Cited by 690 · see citing works
Interstitial dendritic cell guidance by haptotactic chemokine gradients
Weber, M., Hauschild, R., Schwarz, J., Moussion, C., de Vries, I., Legler, D. F., Luther, S. A., Bollenbach, T., & Sixt, M. (2013) · Science · doi:10.1126/science.1228456 · Cited by 555 · see citing works
Chemokine receptor CCR7 required for T lymphocyte exit from peripheral tissues
Debes, G. F., Arnold, C. N., Young, A. J., Krautwald, S., Lipp, M., Hay, J. B., & Butcher, E. C. (2005) · Nature Immunology · doi:10.1038/ni1238 · Cited by 478 · see citing works
Salman, R. A., M, W. P. A. N. E. T. H. H. H. A., Davenport Richard, J., et al. (2007) · doi:10.3760/cma.j.issn.1007-9742.2007.02.122 · Cited by 475 · see citing works
Lymphatic Vessel Network Structure and Physiology
Breslin, J. W., Yang, Y., Scallan, J. P., Sweat, R. S., Adderley, S., & Murfee, W. L. (2018) · Comprehensive physiology · doi:10.1002/cphy.c180015 · Cited by 402 · see citing works
Lymphangiogenic factors, mechanisms, and applications
Zheng, W., Aspelund, A., & Alitalo, K. K. (2014) · Journal of Clinical Investigation · doi:10.1172/jci71603 · Cited by 318 · see citing works
Fassbender, K. C. (2001) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.70.4.534 · Cited by 302 · see citing works
Hemoglobin and heme scavenging
Ascenzi, P., Bocedi, A., Visca, P., Altruda, F., Tolosano, E., Beringhelli, T., & Fasano, M. (2005) · IUBMB Life (International Union of Biochemistry and Molecular Biology: Life) · doi:10.1080/15216540500380871 · Cited by 280 · see citing works
Inflammation and Lymphatic Function
Schwager, S., & Detmar, M. J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00308 · Cited by 268 · see citing works
Etminan, N., Vergouwen, M. D. I., Ilodigwe, D., et al. (2011) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.7 · Cited by 235 · see citing works
Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1
Schallner, N., Pandit, R., LeBlanc, R. H., Thomas, A. J., Ogilvy, C. S., Zuckerbraun, B. S., Gallo, D. J., Otterbein, L. E., & Hanafy, K. A. (2015) · Journal of Clinical Investigation · doi:10.1172/jci78443 · Cited by 214 · see citing works
Hsu, M., Rayasam, A., Kijak, J. A., Choi, Y. H., Harding, J. S., Marcus, S. A., Karpus, W. J., Sándor, M., & Fábry, Z. (2019) · Nature Communications · doi:10.1038/s41467-018-08163-0 · Cited by 208 · see citing works
Reilly, C. E., Amidei, C., Tolentino, J., Jahromi, B. S., & Macdonald, R. L. (2004) · Journal of neurosurgery · doi:10.3171/jns.2004.101.2.0255 · Cited by 199 · see citing works
Deep cervical lymph node ligation aggravates AD‐like pathology of APP/PS1 mice
Wang, L., Zhang, Y., Zhao, Y., Marshall, C., Wu, T., & Xiao, M. (2019) · Brain Pathology · doi:10.1111/bpa.12656 · Cited by 199 · see citing works
Self-citationNeuroinflammation as a Target for Intervention in Subarachnoid Hemorrhage
Manoel, A. L. D. O., & Macdonald, R. L. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00292 · Cited by 179 · see citing works
Guo, R., Zhou, Q., Proulx, S. T., Wood, R. W., Ji, R., Ritchlin, C. T., Pytowski, B., Zhu, Z., Wang, Y., Schwarz, E. M., et al. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24764 · Cited by 175 · see citing works
Self-citationAntiplatelet therapy for aneurysmal subarachnoid haemorrhage
Mees, S. M. D., van den Bergh, W. M., Algra, A., & Rinkel, G. J. E. (2007) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd006184.pub2 · Cited by 156 · see citing works
Microglia inflict delayed brain injury after subarachnoid hemorrhage
Schneider, U. C., Davids, A., Brandenburg, S., Müller, A., Elke, A., Magrini, S., Atangana, E. N., Turkowski, K., Finger, T., Gutenberg, A., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1440-1 · Cited by 152 · see citing works
Inflammation and Cerebral Vasospasm After Subarachnoid Hemorrhage
Pradilla, G., Chaichana, K. L., Hoang, S., Huang, J., & Tamargo, R. J. (2010) · Neurosurgery Clinics of North America · doi:10.1016/j.nec.2009.10.008 · Cited by 152 · see citing works
Targeting lymphatic function as a novel therapeutic intervention for rheumatoid arthritis
Bouta, E. M., Bell, R. D., Rahimi, H., Xing, L., Wood, R. W., Bingham, C. O., Ritchlin, C. T., & Schwarz, E. M. (2018) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2017.205 · Cited by 147 · see citing works
Self-citationvan Lessen, M., Shibata-Germanos, S., van Impel, A., Hawkins, T. A., Rihel, J., & Schulte‐Merker, S. (2017) · eLife · doi:10.7554/elife.25932 · Cited by 134 · see citing works
Chen, J., He, J., Ni, R., Yang, Q., Zhang, Y., & Luo, L. (2019) · Developmental Cell · doi:10.1016/j.devcel.2019.03.022 · Cited by 132 · see citing works
Self-citationZhou, Q., Guo, R., Wood, R. W., Boyce, B. F., Liang, Q., Wang, Y., Schwarz, E. M., & Xing, L. (2011) · Arthritis & Rheumatism · doi:10.1002/art.30421 · Cited by 128 · see citing works
Self-citationImpaired meningeal lymphatic vessel development worsens stroke outcome.
Yanev, P., Poinsatte, K., Hominick, D., Khurana, N., Zuurbier, K. R., Berndt, M., Plautz, E. J., Dellinger, M. T., & Stowe, A. M. (2020) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x18822921 · Cited by 126 · see citing works
Wilson, C. D., Safavi‐Abbasi, S., Sun, H., Kalani, M. Y. S., Zhao, Y. D., Levitt, M. R., Hanel, R. A., Sauvageau, E. A., Mapstone, T. B., Albuquerque, F. C., et al. (2016) · Journal of neurosurgery · doi:10.3171/2015.11.jns152094 · Cited by 122 · see citing works
An introduction to the pathophysiology of aneurysmal subarachnoid hemorrhage
van Lieshout, J. H., Dibué, M., Cornelius, J. F., Slotty, P. J., Schneider, T., Restin, T., Boogaarts, H. D., Steiger, H., Petridis, A. K., & Kamp, M. A. (2017) · Neurosurgical Review · doi:10.1007/s10143-017-0827-y · Cited by 119 · see citing works
Massicotte, E. M., & Bigio, M. R. D. (1999) · Journal of neurosurgery · doi:10.3171/jns.1999.91.1.0080 · Cited by 115 · see citing works
Mechanisms of chylomicron uptake into lacteals
Dixon, J. B. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05716.x · Cited by 112 · see citing works
The intrathecal CD163‐haptoglobin–hemoglobin scavenging system in subarachnoid hemorrhage
Galea, J. P., Cruickshank, G. S., Teeling, J. L., Boche, D., Garland, P., Perry, V. H., & Galea, I. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07716.x · Cited by 110 · see citing works
Atangana, E. N., Schneider, U. C., Blecharz, K., et al. (2016) · Translational Stroke Research · doi:10.1007/s12975-016-0485-3 · Cited by 110 · see citing works
Li, R., Liu, W., Yin, J., Chen, Y., Guo, S., Fan, H., Li, X., Zhang, X., He, X., & Duan, C. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1279-1 · Cited by 110 · see citing works
Self-citationZhou, Q., Wood, R. W., Schwarz, E. M., Wang, Y., & Xing, L. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27464 · Cited by 102 · see citing works
Self-citationLeukocyte-endothelial cell interactions in chronic vasospasm after subarachnoid hemorrhage
Gallia, G. L., & Tamargo, R. J. (2006) · Neurological Research · doi:10.1179/016164106x152025 · Cited by 96 · see citing works
A tissue‐engineered model of the intestinal lacteal for evaluating lipid transport by lymphatics
Dixon, J. B., Raghunathan, S., & Swartz, M. A. (2009) · Biotechnology and Bioengineering · doi:10.1002/bit.22337 · Cited by 88 · see citing works
Yao, Z., Wen, Y.-R., Yang, J.-H., & Wang, X. (2018) · Neural Regeneration Research · doi:10.4103/1673-5374.230299 · Cited by 88 · see citing works
A murine model of subarachnoid hemorrhage-induced cerebral vasospasm
Lin, C., Çalışaneller, T., Ukita, N., et al. (2003) · Journal of Neuroscience Methods · doi:10.1016/s0165-0270(02)00344-8 · Cited by 84 · see citing works
A study of blood coagulation and fibrinolytic system in spontaneous subarachnoid hemorrhage
Nina, P., Schisano, G., Chiappetta, F., et al. (2001) · Surgical Neurology · doi:10.1016/s0090-3019(01)00402-5 · Cited by 83 · see citing works
Goodman, J. R., Adham, Z. O., Woltjer, R. L., Lund, A. W., & Iliff, J. J. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.07.020 · Cited by 70 · see citing works
Liang, Q., Ju, Y., Chen, Y., Wang, W., Li, J., Zhang, L. R., Xu, H., Wood, R. W., Schwarz, E. M., Boyce, B. F., et al. (2016) · Arthritis Research & Therapy · doi:10.1186/s13075-016-0963-8 · Cited by 65 · see citing works
Self-citationGarland, P., Durnford, A. J., Okemefuna, A. I., et al. (2016) · Stroke · doi:10.1161/strokeaha.115.011956 · Cited by 61 · see citing works
Xu, Z., Shi, W., Xu, L., Shao, M., Chen, Z.-P., Zhu, G.-C., & Hou, Q. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00298 · Cited by 59 · see citing works
Kasuya, H., Shimizu, T., Okada, T., et al. (1988) · Acta Neurochirurgica · doi:10.1007/bf01424566 · Cited by 48 · see citing works
Acute small intestinal inflammation results in persistent lymphatic alterations
Rehal, S., Stephens, M., Roizes, S., Liao, S., & von der Weid, P. (2018) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00340.2017 · Cited by 43 · see citing works
Becker, F., Kurmaeva, E., Gavins, F. N. E., Stevenson, E. V., Navratil, A. R., Jin, L., Tsunoda, I., Orr, A. W., Alexander, J. S., & Ostanin, D. V. (2016) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000731 · Cited by 34 · see citing works
Wang, X., Zhao, J., & Qin, L. (2017) · Europe PMC (PubMed Central) · Cited by 34 · see citing works
Lymphatic imaging to assess rheumatoid flare: mechanistic insights and biomarker potential
Rahimi, H., Bell, R. D., Bouta, E. M., Wood, R. W., Xing, L., Ritchlin, C. T., & Schwarz, E. M. (2016) · Arthritis Research & Therapy · doi:10.1186/s13075-016-1092-0 · Cited by 32 · see citing works
Self-citationNarimatsu, A., Hattori, T., Koike, N., Tajima, K., Nakagawa, H., Yamakawa, N., Usui, Y., Kumakura, S., Matsumoto, T., & Gotô, H. (2019) · Scientific Reports · doi:10.1038/s41598-019-39876-x · Cited by 32 · see citing works
Macrophage CD163 expression in cerebrospinal fluid: association with subarachnoid hemorrhage outcome
Thomas, A. J., Ogilvy, C. S., Griessenauer, C. J., & Hanafy, K. A. (2018) · Journal of neurosurgery · doi:10.3171/2018.2.jns172828 · Cited by 27 · see citing works
Lymphangiogenesis is increased in heart valve endocarditis
Niinimäki, E., Mennander, A., Paavonen, T., et al. (2016) · International Journal of Cardiology · doi:10.1016/j.ijcard.2016.06.049 · Cited by 26 · see citing works
Park, J.-H., Park, Y. S., Suk, J.-S., et al. (2011) · Journal of Neurosurgery Pediatrics · doi:10.3171/2011.8.peds1190 · Cited by 20 · see citing works
Zhang, Y., Daubel, N., Stritt, S., & Mäkinen, T. (2018) · Development · doi:10.1242/dev.156745 · Cited by 20 · see citing works
Wang, X., Zhao, J. J., Qin, L., et al. (2016) · PubMed · Cited by 12 · see citing works
Chen, J., He, J., Yang, Q., Zhang, Y., & Luo, L. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/346007 · Cited by 9 · see citing works
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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
Dong, H., Dai, X., Zhou, Y., Shi, C., Bhuiyan, P., Sun, Z., Li, N., & Jin, W. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03028-4 · Cited by 27 · see citing works
- Authors
- Chen, J., Wang, L., Xu, H., Xing, L., Zhuang, Z., Zheng, Y., Li, X., Wang, C., Chen, S., Guo, Z., Liang, Q., & Wang, Y.
- Affiliations
- Shanghai University of Traditional Chinese Medicine (CN)
- University of Rochester Medicine (US)
- Nanjing University of Chinese Medicine (CN)
- Guangzhou University of Chinese Medicine (CN)
- Corresponding author
- Liang, Qianqian
- Wang, Yongjun
- ORCID
- Venue
- Nature Communications
- Published
- 2020-06-22
- Volume
- 11
- Issue
- 1
- Pages
- 3159-3159
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7308412
- OpenAlex
- W3036204389
- Cited by
- 208
- References
- 60
- Citations by year
- 2026: 34 · 2025: 28 · 2024: 40 · 2023: 39 · 2022: 32 · 2021: 30 · 2020: 3 · 2019: 1
- FWCI
- 11.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fudan University
- Shanghai Municipal Education Commission (19SG39, 2018-2020)
- National Institute on Aging (R01AG059775)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- meningeal lymphatic vessels, subarachnoid hemorrhage, erythrocyte clearance, cerebrospinal fluid, cervical lymph nodes, lymph flow, neuroinflammation, neurological deficit, lymphangiogenesis, lymphangiectasia, mouse model
- MeSH terms
- Animals, Brain Injuries, Erythrocytes, Lymph Nodes, Lymphatic System, Male, Meninges, Meningitis, Mice, Inbred C57BL, Neck, Subarachnoid Hemorrhage, Models, Animal, Vascular Endothelial Growth Factor Receptor-3, Lymphangiogenesis, Lymphatic Vessels, Mice
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