{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T07:26:28Z","timestamp":1777793188034,"version":"3.51.4"},"reference-count":46,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2007,8,8]],"date-time":"2007-08-08T00:00:00Z","timestamp":1186531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2008,2]]},"abstract":"<jats:p>The proinflammatory cytokine interleukin (IL)-1 mediates several forms of experimentally induced acute brain injury and has been implicated in chronic neurodegenerative disorders. The IL-1 receptor antagonist, IL-1RA, protects rodents against ischaemic brain injury, but its molecular mass (17 kDa) potentially limits the brain penetration of peripherally administered IL-1RA. We therefore sought to identify whether therapeutically effective concentrations of IL-1RA in the rat were also achieved in brain of patients with subarachnoid haemorrhage (SAH), using a peripheral administration regime that had proved to be safe and reduce peripheral inflammation in patients after stroke. An intravenous bolus of IL-1RA, followed by infusion, was administered to rats after induction of focal cerebral ischaemia. The effects of IL-1RA on brain ischaemia and the concentrations achieved in cerebrospinal fluid (CSF), were determined. Interleukin-1 receptor antagonist was similarly administered to patients with SAH, and CSF was sampled via external ventricular drains. In rats, IL-1RA significantly reduced brain injury induced by focal cerebral ischaemia. The plasma IL-1RA concentrations reached 12\u00b12 \u03bcg\/mL by 30 mins, and CSF concentrations were maintained between 91 and 232 ng\/mL between 1 and 24 h of infusion. In patients with SAH, IL-1RA reached a steady-state plasma concentration of 22 \u00b1 4 \u03bcg\/mL by 15 mins, and CSF concentrations were maintained at 78 to 558 ng\/mL between 1 and 24 h. Intravenous delivery of IL-1RA leads to CSF concentrations in patients comparable to those that are neuroprotective in rats, and might therefore be of therapeutic benefit.<\/jats:p>","DOI":"10.1038\/sj.jcbfm.9600537","type":"journal-article","created":{"date-parts":[[2007,8,8]],"date-time":"2007-08-08T03:28:23Z","timestamp":1186543703000},"page":"387-394","source":"Crossref","is-referenced-by-count":94,"title":["Interleukin-1 Receptor Antagonist Penetrates Human Brain at Experimentally Therapeutic Concentrations"],"prefix":"10.1177","volume":"28","author":[{"given":"Simon R","family":"Clark","sequence":"first","affiliation":[{"name":"Stroke Services, Hope Hospital, Salford, UK"},{"name":"Faculty of Life Sciences, University of Manchester, Manchester, UK"},{"name":"Department of Neurosurgery, Walton Centre for Neurology and Neurosurgery, Fazakerley Liverpool, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine J","family":"McMahon","sequence":"additional","affiliation":[{"name":"Stroke Services, Hope Hospital, Salford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iva","family":"Gueorguieva","sequence":"additional","affiliation":[{"name":"Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm","family":"Rowland","sequence":"additional","affiliation":[{"name":"Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia","family":"Scarth","sequence":"additional","affiliation":[{"name":"Injury Research, Hope Hospital, Salford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Georgiou","sequence":"additional","affiliation":[{"name":"Stroke Services, Hope Hospital, Salford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pippa J","family":"Tyrrell","sequence":"additional","affiliation":[{"name":"Stroke Services, Hope Hospital, Salford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen J","family":"Hopkins","sequence":"additional","affiliation":[{"name":"Injury Research, Hope Hospital, Salford, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy J","family":"Rothwell","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences, University of Manchester, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2007,8,8]]},"reference":[{"key":"bibr1-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1981.tb04421.x"},{"key":"bibr2-sj.jcbfm.9600537","doi-asserted-by":"crossref","unstructured":"Allan SM, Rothwell NJ (2003) Inflammation in central nervous system injury. Philos Trans R Soc Lond B Biol Sci (1438, ed), 1669\u201377","DOI":"10.1098\/rstb.2003.1358"},{"key":"bibr3-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1038\/nri1664"},{"key":"bibr4-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(96)00815-3"},{"key":"bibr5-sj.jcbfm.9600537","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.4049\/jimmunol.156.7.2534","volume":"156","author":"Colotta F","year":"1996","journal-title":"J Immunol"},{"key":"bibr6-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0173(97)00014-3"},{"key":"bibr7-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-7-5"},{"key":"bibr8-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.054882"},{"key":"bibr9-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1994.03510470040032"},{"key":"bibr10-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1227\/00006123-198001000-00001"},{"key":"bibr11-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1002\/art.10870"},{"key":"bibr12-sj.jcbfm.9600537","first-page":"1477","volume":"147","author":"Garcia JH","year":"1995","journal-title":"Am J Pathol"},{"key":"bibr13-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1007\/s007010050472"},{"key":"bibr14-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000048846.09677.62"},{"key":"bibr15-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1016\/1043-4666(92)90078-6"},{"key":"bibr16-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1097\/00008506-200010000-00001"},{"key":"bibr17-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(94)90005-1"},{"key":"bibr18-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1038\/343336a0"},{"key":"bibr19-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1088\/0967-3334\/26\/4\/008"},{"key":"bibr20-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.44.275"},{"key":"bibr21-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb08310.x"},{"key":"bibr22-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052980"},{"key":"bibr23-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.4.1431"},{"key":"bibr24-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6436"},{"key":"bibr25-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1097\/00006123-200207000-00024"},{"key":"bibr26-sj.jcbfm.9600537","doi-asserted-by":"crossref","unstructured":"Mahoney FI, Barthel DW (1965) Functional evaluation: the Barthel index. Maryland State Med J 61\u20135","DOI":"10.1037\/t02366-000"},{"key":"bibr27-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1994.1215"},{"key":"bibr28-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705462"},{"key":"bibr29-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1002\/art.10578"},{"key":"bibr30-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199707000-00010"},{"key":"bibr31-sj.jcbfm.9600537","first-page":"159","volume":"53","author":"O'Shea M","year":"2004","journal-title":"West Indian Med J"},{"key":"bibr32-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(97)00214-1"},{"key":"bibr33-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2003.98.5.1040"},{"key":"bibr34-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20308"},{"key":"bibr35-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20021098"},{"key":"bibr36-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.1996.0059"},{"key":"bibr37-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(92)90033-T"},{"key":"bibr38-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119808"},{"key":"bibr39-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(08)60724-2"},{"key":"bibr40-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.51.11.1457"},{"key":"bibr41-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(74)91639-0"},{"key":"bibr42-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03872.x"},{"key":"bibr43-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)01343-G"},{"key":"bibr44-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(99)00202-7"},{"key":"bibr45-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.19.5.604"},{"key":"bibr46-sj.jcbfm.9600537","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.20.1.84"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/sj.jcbfm.9600537","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1038\/sj.jcbfm.9600537","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1038\/sj.jcbfm.9600537","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:09:37Z","timestamp":1777493377000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1038\/sj.jcbfm.9600537"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8,8]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,2]]}},"alternative-id":["10.1038\/sj.jcbfm.9600537"],"URL":"https:\/\/doi.org\/10.1038\/sj.jcbfm.9600537","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8,8]]}}}