{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T23:25:03Z","timestamp":1791761103114,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS072497"],"award-info":[{"award-number":["R01 NS072497"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS043295"],"award-info":[{"award-number":["NS043295"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Our objective is to explore whether blood\u2013cerebrospinal fluid (CSF) barrier biomarkers differ in episodic migraine (EM) or chronic migraine (CM) from controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Reports of blood\u2013brain barrier and blood\u2013cerebrospinal fluid barrier (BCSFB) disruption in migraine vary. Our hypothesis is that investigation of biomarkers associated with blood, CSF, brain, cell adhesion, and inflammation will help elucidate migraine pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We recruited 14 control volunteers without headache disorders and 42 individuals with EM or CM as classified using the International Classification of Headache Disorders, 3rd edition, criteria in a cross\u2010sectional study located at our Pasadena and Stanford headache research centers in California. Blood and lumbar CSF samples were collected once from those diagnosed with CM or those with EM during two states: during a typical migraine, before rescue therapy, with at least 6\/10 level of pain (ictal); and when migraine free for at least 48\u00a0h (interictal). The average number of headaches per month over the previous year was estimated by those with EM; this enabled comparison of biomarker changes between controls and three headache frequency groups: &lt;2 per month, 2\u201314 per month, and CM. Blood and CSF biomarkers were determined using antibody\u2010based methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Antimigraine medication was only taken by the EM and CM groups. Compared to controls, the migraine group had significantly higher mean CSF\u2013blood quotients of albumin (\n                      <jats:italic>Q<\/jats:italic>\n                      <jats:sub>alb<\/jats:sub>\n                      : mean\u00a0\u00b1\u00a0standard deviation (SD): 5.6\u00a0\u00b1\u00a02.3 vs. 4.1\u00a0\u00b1\u00a01.9) and fibrinogen (\n                      <jats:italic>Q<\/jats:italic>\n                      <jats:sub>fib<\/jats:sub>\n                      mean\u00a0\u00b1\u00a0SD: 1615\u00a0\u00b1\u00a099.0 vs. 86.1\u00a0\u00b1\u00a055.0). Mean CSF but not plasma soluble vascular cell adhesion molecule\u20101 (sVCAM\u20101) levels were significantly higher in those with more frequent migraine: (4.5\u00a0ng\/mL\u00a0\u00b1\u00a01.1 in those with &lt;2 headache days a month; 5.5\u00a0\u00b1\u00a01.9 with 2\u201314\u00a0days a month; and 7.1\u00a0\u00b1\u00a02.9 in CM), while the\n                      <jats:italic>Q<\/jats:italic>\n                      <jats:sub>fib<\/jats:sub>\n                      ratio was inversely related to headache frequency. We did not find any difference in individuals with EM or CM from controls for CSF cell count, total protein, matrix metalloproteinase\u20109, soluble platelet\u2010derived growth factor receptor \u03b2, tumor necrosis factor\u2010alpha, interferon\u2010gamma, interleukin (IL)\u20106, IL\u20108, IL\u201010, or C\u2010reactive protein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The higher\n                      <jats:italic>Q<\/jats:italic>\n                      <jats:sub>alb<\/jats:sub>\n                      and\n                      <jats:italic>Q<\/jats:italic>\n                      <jats:sub>fib<\/jats:sub>\n                      ratios may indicate that the transport of these blood\u2010derived proteins is disturbed at the BCSFB in persons with migraine. These changes most likely occur at the choroid plexus epithelium, as there are no signs of typical endothelial barrier disruption. The most striking finding in this hypothesis\u2010generating study of migraine pathophysiology is that sVCAM\u20101 levels in CSF may be a biomarker of higher frequency of migraine and CM. An effect from migraine medications cannot be excluded, but there is no known mechanism to suggest they have a role in altering the CSF biomarkers.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14088","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T08:11:33Z","timestamp":1615882293000},"page":"536-545","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Evidence that blood\u2013CSF barrier transport, but not inflammatory biomarkers, change in migraine, while CSF sVCAM1 associates with migraine frequency and CSF fibrinogen"],"prefix":"10.1111","volume":"61","author":[{"given":"Robert P.","family":"Cowan","sequence":"first","affiliation":[{"name":"Department of Neurology Stanford University Palo Alto CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah B.","family":"Gross","sequence":"additional","affiliation":[{"name":"Neurosciences Huntington Medical Research Institutes Pasadena CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie D.","family":"Sweeney","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience Zilkha Neurogenetic Institute Keck School of Medicine University of Southern California Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay P.","family":"Sagare","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience Zilkha Neurogenetic Institute Keck School of Medicine University of Southern California Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Montagne","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience Zilkha Neurogenetic Institute Keck School of Medicine University of Southern California Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianghong","family":"Arakaki","sequence":"additional","affiliation":[{"name":"Neurosciences Huntington Medical Research Institutes Pasadena CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred N.","family":"Fonteh","sequence":"additional","affiliation":[{"name":"Neurosciences Huntington Medical Research Institutes Pasadena CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berislav V.","family":"Zlokovic","sequence":"additional","affiliation":[{"name":"Department of Physiology and Neuroscience Zilkha Neurogenetic Institute Keck School of Medicine University of Southern California Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice M.","family":"Pogoda","sequence":"additional","affiliation":[{"name":"Cipher Biostatistics &amp; Reporting Reno NV USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Harrington","sequence":"additional","affiliation":[{"name":"Neurosciences Huntington Medical Research Institutes Pasadena CA USA"},{"name":"Department of Physiology and Neuroscience Zilkha Neurogenetic Institute Keck School of Medicine University of Southern California Los Angeles CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00034.2015"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0035-3787(05)85108-2"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2007.03.012"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0511-10.2010"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx089"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww097"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.2001.041007629.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.01.029"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00050.2017"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1807-1"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1985.49"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.11.031"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-020-00196-2"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww096"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13341"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2007.01369.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000176298.63840.99"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25731"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2007.00958.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200421227"},{"issue":"1","key":"e_1_2_10_22_1","first-page":"99","article-title":"Increased permeability of the blood\u2010brain barrier following administration of glyceryl trinitrate in common carp (Cyprinus carpio L.)","volume":"32","author":"Kovacic S","year":"2008","journal-title":"Coll Antropol"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13281"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2019.06.001"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413485658"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2006.00445.x"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.12.032"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0297-y"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4288"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458515601903"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102410383589"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3598"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.08.029"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep11412"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0440-4"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199803)28:03<995::AID-IMMU995>3.0.CO;2-D"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0128870"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102411408360"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2009.01551.x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.07.004"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3265"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.02.012"},{"issue":"6","key":"e_1_2_10_43_1","first-page":"1819","article-title":"ICAM\u20101, VCAM\u20101, and MAdCAM\u20101 are expressed on choroid plexus epithelium but not endothelium and mediate binding of lymphocytes in vitro","volume":"148","author":"Steffen BJ","year":"1996","journal-title":"Am J Pathol"}],"container-title":["Headache: The Journal of Head and Face Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/head.14088","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/head.14088","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/head.14088","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T11:51:37Z","timestamp":1762084297000},"score":1,"resource":{"primary":{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/10.1111\/head.14088"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":42,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1111\/head.14088"],"URL":"https:\/\/doi.org\/10.1111\/head.14088","archive":["Portico"],"relation":{},"ISSN":["0017-8748","1526-4610"],"issn-type":[{"value":"0017-8748","type":"print"},{"value":"1526-4610","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"2020-08-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}