{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:11:14Z","timestamp":1788315074040,"version":"build-2803163510"},"reference-count":62,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"36","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,9,6]]},"abstract":"<jats:p>Cerebrospinal fluid (CSF) is responsible for maintaining brain homeostasis through nutrient delivery and waste removal for the central nervous system (CNS). Here, we demonstrate extensive CSF flow throughout the peripheral nervous system (PNS) by tracing distribution of multimodal 1.9-nanometer gold nanoparticles, roughly the size of CSF circulating proteins, infused within the lateral cerebral ventricle (a primary site of CSF production). CSF-infused 1.9-nanometer gold transitions from CNS to PNS at root attachment\/transition zones and distributes through the perineurium and endoneurium, with ultimate delivery to axoplasm of distal peripheral nerves. Larger 15-nanometer gold fails to transit from CNS to PNS and instead forms \u201cdye-cuffs,\u201d as predicted by current dogma of CSF restriction within CNS, identifying size limitations in central to peripheral flow. Intravenous 1.9-nanometer gold is unable to cross the blood-brain\/nerve barrier. Our findings suggest that CSF plays a consistent role in maintaining homeostasis throughout the nervous system with implications for CNS and PNS therapy and neural drug delivery.<\/jats:p>","DOI":"10.1126\/sciadv.adn3259","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T18:00:13Z","timestamp":1725472813000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":47,"title":["Cerebrospinal fluid flow extends to peripheral nerves further unifying the nervous system"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5624-4763","authenticated-orcid":true,"given":"Alexander P.","family":"Ligocki","sequence":"first","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6112-1015","authenticated-orcid":true,"given":"Augustine V.","family":"Vinson","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6971-0698","authenticated-orcid":true,"given":"Anthony T.","family":"Yachnis","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine, Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"William A.","family":"Dunn","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine, Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, FL 32611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas E.","family":"Smith","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Scott","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimena V.","family":"Alvarez-Castanon","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9983-6986","authenticated-orcid":true,"given":"Daniel E.","family":"Baez Montalvo","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1746-3415","authenticated-orcid":true,"given":"Olivia G.","family":"Frisone","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5946-9362","authenticated-orcid":true,"given":"Gary A. J.","family":"Brown","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel E.","family":"Pessa","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5668-1795","authenticated-orcid":true,"given":"Edward W.","family":"Scott","sequence":"additional","affiliation":[{"name":"Program in Stem Cell Biology and Regenerative Medicine, Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32611, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","first-page":"93","article-title":"Studies on cerebro-spinal fluid. No. IV: The dual source of cerebro-spinal fluid","volume":"31","author":"Weed L.","year":"1914","unstructured":"L. Weed, Studies on cerebro-spinal fluid. No. IV: The dual source of cerebro-spinal fluid. J. Med. Res. 31, 93\u2013118.11 (1914).","journal-title":"J. Med. Res."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-020-03706-5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90603"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.anorl.2011.03.002"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003748"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14432"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01484-6"},{"key":"e_1_3_2_9_2","unstructured":"A. C. Guyton J. E. Hall Textbook of Medical Physiology (E. Saunders ed. 11 2005) pp. 764\u2013767."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8454-5-10"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00031.2020"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8454-2-6"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1809-z"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.12.040"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900838"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-010-0783-x"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-938-3_6"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00227759"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.13.3.203"},{"key":"e_1_3_2_20_2","first-page":"153","article-title":"The connexions of the spinal sub-arachnoid space with the lymphatic system","volume":"82","author":"Brierley J.","year":"1948","unstructured":"J. Brierley, E. Field, The connexions of the spinal sub-arachnoid space with the lymphatic system. J. Anat. 82, 153\u2013166 (1948).","journal-title":"J. Anat."},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00294304"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/354411a0"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.12.037"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp5034068"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(01)76211-X"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1259\/bjr\/13169882"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.67.031103.154845"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1863-09.2009"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pep.2015.09.023"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/nn800508f"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1515"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.03.029"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-82599-1"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36083-1"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-015-1581-6"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00320.x"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aav5447"},{"key":"e_1_3_2_38_2","first-page":"153","article-title":"Zur Physiologie der Cerebrospinalfluessigkeit","author":"Quincke H.","year":"1872","unstructured":"H. Quincke, Zur Physiologie der Cerebrospinalfluessigkeit. Arch. Anat. Physiol. Wiss Med. 153\u2013177 (1872).","journal-title":"Arch. Anat. Physiol. Wiss Med."},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07318-3"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1091640102"},{"key":"e_1_3_2_41_2","first-page":"R88","article-title":"Determination of volumetric cerebrospinal fluid absorption into extracranial lymphatics in sheep","volume":"274","author":"Boulton M.","year":"1998","unstructured":"M. Boulton, M. Flessner, D. Armstrong, J. Hay, M. Johnston, Determination of volumetric cerebrospinal fluid absorption into extracranial lymphatics in sheep. Am. J. Physiol. 274, R88\u2013R96 (1998).","journal-title":"Am. J. Physiol."},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06899-4"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00500-9"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01029-1"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.adc8810"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.40.3.648"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.34.1.207"},{"key":"e_1_3_2_48_2","first-page":"71","article-title":"Evidence for passage of cerebrospinal fluid among spinal nerves","volume":"98","author":"Steer J. C.","year":"1968","unstructured":"J. C. Steer, F. Horney, Evidence for passage of cerebrospinal fluid among spinal nerves. Can. Med. Assoc. J. 98, 71\u201374 (1968).","journal-title":"Can. Med. Assoc. J."},{"key":"e_1_3_2_49_2","first-page":"1087","article-title":"Abstract of a lecture on pernicious an\u00e6mia","volume":"22","author":"Quincke H.","year":"1877","unstructured":"H. Quincke, J. Gunn, Abstract of a lecture on pernicious an\u00e6mia. Edinb. Med. J. 22, 1087\u20131098 (1877).","journal-title":"Edinb. Med. J."},{"key":"e_1_3_2_50_2","unstructured":"L. N. Telano S. Baker Physiology cerebral spinal fluid in StatPearls [StatPearls Publishing Treasure Island (FL) 2024]."},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.1999.19420161.x"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00687488"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00342622"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00687240"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1253"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-020-00230-3"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneng.2013.00007"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20990"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(88)90233-6"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.04.003"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111320"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2015.07.027"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108524"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adn3259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T18:03:09Z","timestamp":1725472989000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adn3259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,6]]},"references-count":62,"journal-issue":{"issue":"36","published-print":{"date-parts":[[2024,9,6]]}},"alternative-id":["10.1126\/sciadv.adn3259"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adn3259","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,6]]},"assertion":[{"value":"2023-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadn3259"}}