{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:28:12Z","timestamp":1768566492438,"version":"3.49.0"},"posted":{"date-parts":[[2023,12,7]]},"group-title":"Neurology","reference-count":49,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec id=\"s21\">\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The inflammatory response within the central nervous system is a key driver of secondary brain injury after hemorrhagic stroke, both in patients with intracerebral hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to characterize inflammatory molecules in the blood and cerebrospinal fluid (CSF) of patients within 72 hours of hemorrhage to understand how such molecules vary across disease types and disease severity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec id=\"s22\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Biological samples were collected from patients admitted to a single-center Neurosciences Intensive Care Unit with a diagnosis of ICH or aSAH between 2014 and 2022. Control CSF samples were collected from patients undergoing CSF diversion for normal pressure hydrocephalus. A panel of immune molecules in the plasma and CSF samples was analyzed using Cytometric Bead Array assays. Clinical variables, including demographics, disease severity, and intensive care unit length of stay were collected.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec id=\"s23\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Plasma and\/or CSF samples were collected from 260 patients (188 ICH patients, 54 aSAH patients, 18 controls). C-C motif chemokine ligand-2 (CCL2), interleukin-6 (IL-6), granulocyte-colony stimulating factor (G-CSF), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF), were detectable in the CSF within the first 3 days after hemorrhage, and all were elevated compared to plasma. Compared with controls, CCL2, IL-6, IL-8, G-CSF, and VEGF were elevated in the CSF of both ICH and aSAH patients (p&lt;0.01 for all comparisons). VEGF was increased in ICH patients compared to aSAH patients (p&lt;0.01). CCL2, G-CSF, and VEGF in the CSF were associated with more severe disease in aSAH patients only.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec id=\"s24\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Within 3 days of hemorrhagic stroke, proinflammatory molecules can be detected in the CSF at higher concentrations than in the plasma. Early concentrations of some pro-inflammatory molecules may be associated with markers of disease severity.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.12.05.23299566","type":"posted-content","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T17:45:15Z","timestamp":1701971115000},"source":"Crossref","is-referenced-by-count":0,"title":["Characterization of CSF inflammatory markers after hemorrhagic stroke and their relationship to disease severity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6506-6017","authenticated-orcid":false,"given":"Jessica","family":"Magid-Bernstein","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison L.","family":"Herman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zili","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conor W.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Beatty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5954-3518","authenticated-orcid":false,"given":"Sofia","family":"Velazquez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eitan","family":"Neeman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6407-0302","authenticated-orcid":false,"given":"Guido","family":"Falcone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3072-6198","authenticated-orcid":false,"given":"Jennifer","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9711-3340","authenticated-orcid":false,"given":"Nils","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4659-6861","authenticated-orcid":false,"given":"Emily J.","family":"Gilmore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3234-9541","authenticated-orcid":false,"given":"Charles","family":"Matouk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2003-5473","authenticated-orcid":false,"given":"Kevin","family":"Sheth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6898-1680","authenticated-orcid":false,"given":"Lauren","family":"Sansing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023120905100518000_2023.12.05.23299566v1.1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.jns.2019.01.013","article-title":"Intracerebral hemorrhage outcome: a comprehensive update","volume":"398","year":"2019","journal-title":"Journal of the Neurologic Sciences"},{"key":"2023120905100518000_2023.12.05.23299566v1.2","first-page":"365","article-title":"Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis","volume":"8","year":"2009","journal-title":"Lancet Neurology"},{"key":"2023120905100518000_2023.12.05.23299566v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70017-5"},{"key":"2023120905100518000_2023.12.05.23299566v1.4","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181dd42b3"},{"key":"2023120905100518000_2023.12.05.23299566v1.5","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51443"},{"key":"2023120905100518000_2023.12.05.23299566v1.6","doi-asserted-by":"publisher","DOI":"10.1161\/hs0901.095677"},{"key":"2023120905100518000_2023.12.05.23299566v1.7","doi-asserted-by":"crossref","first-page":"e693","DOI":"10.1016\/j.wneu.2017.12.148","article-title":"Intraventricular hemorrhage caused by subarachnoid hemorrhage: does the severity matter?","volume":"111","year":"2018","journal-title":"World Neurosurgery"},{"key":"2023120905100518000_2023.12.05.23299566v1.8","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.008470"},{"key":"2023120905100518000_2023.12.05.23299566v1.9","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.535419"},{"key":"2023120905100518000_2023.12.05.23299566v1.10","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.32.4.891"},{"key":"2023120905100518000_2023.12.05.23299566v1.11","doi-asserted-by":"crossref","unstructured":"Agnihotri S , Czap A , Staff I , Fortunato G , McCullough L . Peripheral leukocyte counts and outcomes after intracerebral hemorrhage. Journal of Neuroinflammation. 2011;8:160.","DOI":"10.1186\/1742-2094-8-160"},{"key":"2023120905100518000_2023.12.05.23299566v1.12","doi-asserted-by":"publisher","DOI":"10.3171\/2019.6.JNS19613"},{"key":"2023120905100518000_2023.12.05.23299566v1.13","doi-asserted-by":"crossref","first-page":"e16211","DOI":"10.1097\/MD.0000000000016211","article-title":"Neutrophil-lymphocyte ratio predicts the outcome of intracerebral hemorrhage: A meta-analysis","volume":"98","year":"2019","journal-title":"Medicine"},{"key":"2023120905100518000_2023.12.05.23299566v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.11.019"},{"key":"2023120905100518000_2023.12.05.23299566v1.15","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.115.009880"},{"key":"2023120905100518000_2023.12.05.23299566v1.16","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1582132"},{"key":"2023120905100518000_2023.12.05.23299566v1.17","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9268-1"},{"key":"2023120905100518000_2023.12.05.23299566v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2016.11.131"},{"key":"2023120905100518000_2023.12.05.23299566v1.19","doi-asserted-by":"publisher","DOI":"10.1179\/016164101101199243"},{"key":"2023120905100518000_2023.12.05.23299566v1.20","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-019-00764-1"},{"key":"2023120905100518000_2023.12.05.23299566v1.21","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X211012110"},{"key":"2023120905100518000_2023.12.05.23299566v1.22","doi-asserted-by":"crossref","first-page":"eabd6279","DOI":"10.1126\/sciimmunol.abd6279","article-title":"Longitudinal transcriptomics define the stages of myeloid activation in the living human brain after intracerebral hemorrhage","volume":"6","year":"2021","journal-title":"Science Immunology"},{"key":"2023120905100518000_2023.12.05.23299566v1.23","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122580"},{"key":"2023120905100518000_2023.12.05.23299566v1.24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.2006.00790.x"},{"key":"2023120905100518000_2023.12.05.23299566v1.25","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.27.8.1304"},{"key":"2023120905100518000_2023.12.05.23299566v1.26","first-page":"104","article-title":"A new subarachnoid hemorrhage grading system based on glasgow coma scale: a comparison with the hunt and hess and world federation of neurological surgeons scales in a clinical series","volume":"41","year":"1997","journal-title":"Neurosurgery"},{"key":"2023120905100518000_2023.12.05.23299566v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-63298-9"},{"key":"2023120905100518000_2023.12.05.23299566v1.28","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-017-0930-2"},{"key":"2023120905100518000_2023.12.05.23299566v1.29","first-page":"21","article-title":"Prediction of symptomatic vasospasm after subarachnoid hemorrhage: the modified Fisher scale","volume":"58","year":"2006","journal-title":"Neurosurgery"},{"key":"2023120905100518000_2023.12.05.23299566v1.30","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1968.28.1.0014"},{"key":"2023120905100518000_2023.12.05.23299566v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2019.154778"},{"key":"2023120905100518000_2023.12.05.23299566v1.32","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0675-7"},{"key":"2023120905100518000_2023.12.05.23299566v1.33","doi-asserted-by":"publisher","DOI":"10.3171\/JNS\/2008\/109\/7\/0038"},{"key":"2023120905100518000_2023.12.05.23299566v1.34","doi-asserted-by":"publisher","DOI":"10.3390\/biom11081123"},{"key":"2023120905100518000_2023.12.05.23299566v1.35","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.70.4.534"},{"key":"2023120905100518000_2023.12.05.23299566v1.36","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1993.78.4.0562"},{"key":"2023120905100518000_2023.12.05.23299566v1.37","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1604084"},{"key":"2023120905100518000_2023.12.05.23299566v1.38","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000255440.21495.80"},{"key":"2023120905100518000_2023.12.05.23299566v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-79586-3"},{"key":"2023120905100518000_2023.12.05.23299566v1.40","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-010-9432-4"},{"key":"2023120905100518000_2023.12.05.23299566v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2015.47"},{"key":"2023120905100518000_2023.12.05.23299566v1.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2021.577610"},{"key":"2023120905100518000_2023.12.05.23299566v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2016.88"},{"key":"2023120905100518000_2023.12.05.23299566v1.44","doi-asserted-by":"publisher","DOI":"10.1172\/JCI9369"},{"key":"2023120905100518000_2023.12.05.23299566v1.45","first-page":"2005","article-title":"Granulocyte colony-stimulating factor improves neurological function and nagiogenesis in intracerebral hemorrhage rats","volume":"22","year":"2018","journal-title":"European Review for Medical and Pharmacological Sciences"},{"key":"2023120905100518000_2023.12.05.23299566v1.46","doi-asserted-by":"publisher","DOI":"10.4161\/cc.4.12.2213"},{"key":"2023120905100518000_2023.12.05.23299566v1.47","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-019-0597-7"},{"key":"2023120905100518000_2023.12.05.23299566v1.48","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2015.00048"},{"key":"2023120905100518000_2023.12.05.23299566v1.49","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1997.87.2.0215"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.12.05.23299566","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:46:14Z","timestamp":1768506374000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2023.12.05.23299566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,7]]},"references-count":49,"URL":"https:\/\/doi.org\/10.1101\/2023.12.05.23299566","relation":{},"subject":[],"published":{"date-parts":[[2023,12,7]]},"subtype":"preprint"}}