{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T13:28:52Z","timestamp":1789824532222,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2585,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The efficacy of the free radical trapping agent NXY\u2010059 in reducing the infarct volume following both transient and permanent focal ischaemia has been examined in rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the transient ischaemia model, rats were subjected to a 2\u2003h occlusion of the middle cerebral artery (MCA). Intravenous infusion of NXY\u2010059 (1, 10 and 30\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h) for 21.75\u2003h starting 2.25\u2003h after the occlusion, produced a dose\u2010dependent decrease in both neurological impairment and the histologically measured infarct volume (a mean 59% decrease at 10\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In the permanent ischaemia model, animals were injected (s.c.) with a loading dose of NXY\u2010059 of 32.5, 53.8 or 75.4\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup> and osmotic minipumps were implanted which had been primed to deliver respectively 30, 50 or 70\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003h. When treatment was initiated 5\u2003min after MCA occlusion there was a dose dependent protection of both cortical and sub\u2010cortical tissue (cortex: 63% at the mid\u2010range dose). Protection was related linearly to plasma concentration (plasma unbound NXY\u2010059 concentration at 1\u2003h: 37\u00b116\u2003\u03bcmol\u2003l<jats:sup>\u22121<\/jats:sup> at the mid\u2010range dose).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>When the mid range dose was administered between 5\u2003min\u2003\u2013\u20034\u2003h after MCA occlusion, a marked and statistically significant protection was seen at all time points (44% protection in cortex at 4\u2003h).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data demonstrate the substantial neuroprotective efficacy of NXY\u2010059 at plasma concentrations that can be achieved clinically and indicate that NXY\u2010059 also has a therapeutic window of opportunity that is clinically relevant.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2002) <jats:bold>135<\/jats:bold>, 103\u2013112; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704449\">10.1038\/sj.bjp.0704449<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704449","type":"journal-article","created":{"date-parts":[[2006,6,7]],"date-time":"2006-06-07T19:20:37Z","timestamp":1149708037000},"page":"103-112","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["Effect of NXY\u2010059 on infarct volume after transient or permanent middle cerebral artery occlusion in the rat; studies on dose, plasma concentration and therapeutic time window"],"prefix":"10.1111","volume":"135","author":[{"given":"S G","family":"Sydserff","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A R","family":"Borelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A R","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A J","family":"Cross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(91)90383-Y"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.17.3.472"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)01499-6"},{"key":"e_1_2_7_5_1","first-page":"301","article-title":"Alterations in cerebral endothelial cell function in ischemia","volume":"71","author":"BETZ A.L.","year":"1996","journal-title":"Adv. Neurol."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199911080-00004"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1987.127"},{"key":"e_1_2_7_8_1","first-page":"1477","article-title":"Interleukin\u20101 receptor antagonist decreases the number of necrotic neurons in rats with middle cerebral artery occlusion","volume":"146","author":"CARCIA J.H.","year":"1995","journal-title":"Am. J. Pathol."},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)91689-6"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1991.75.4.0623"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)91424-F"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01229-9"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020221919154"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.08-12-04745.1988"},{"key":"e_1_2_7_15_1","first-page":"281","article-title":"Inflammatory reactions at the blood\u2010endothelial interface in acute stroke","volume":"71","author":"HALLENBECK J.M.","year":"1996","journal-title":"Adv. Neurol."},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(96)00636-1"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1996.0015"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199907000-00008"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.32.3.675"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.31.1.33"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.32.1.190"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(93)90305-Y"},{"key":"e_1_2_7_23_1","first-page":"377","volume-title":"Stroke: Pathophysiology, Diagnosis and Management","author":"MOHR J.P.","year":"1986"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199605000-00014"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.13.5144"},{"key":"e_1_2_7_26_1","volume-title":"The rat brain in stereotaxic co\u2010ordinates","author":"PAXINOS G.","year":"1986"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(00)00170-2"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(90)90093-O"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(92)90033-T"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.2.289"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64052239.x"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1995.120"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb14950.x"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01808631"},{"key":"e_1_2_7_35_1","doi-asserted-by":"crossref","unstructured":"THE NINDS T\u2010PA STROKE STUDY GROUP(1995).Tissue plasminogen activator for acute ischemic stroke.New Engl. J. Med. 333 1581\u20131587.","DOI":"10.1056\/NEJM199512143332401"},{"key":"e_1_2_7_36_1","doi-asserted-by":"crossref","unstructured":"THE NINDS T\u2010PA STROKE STUDY GROUP(1997).Generalized efficacy of t\u2010PA for acute stroke. Subgroup analysis of the NINDS t\u2010PA Stroke Trial.Stroke 28 2119\u20132125.","DOI":"10.1161\/01.STR.28.11.2119"},{"key":"e_1_2_7_37_1","doi-asserted-by":"crossref","unstructured":"THE NINDS T\u2010PA STROKE STUDY GROUP(1999).Effects of tissue plasminogen activator for acute ischemic stroke at one year.New Engl. J. Med. 340 1781\u20131787.","DOI":"10.1056\/NEJM199906103402302"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7364"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.26.8.1438"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1994.tb09816.x"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(01)02618-X"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0704449","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0704449","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0704449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T05:33:21Z","timestamp":1697520801000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0704449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2002,1]]}},"alternative-id":["10.1038\/sj.bjp.0704449"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0704449","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,1]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}