{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:31:10Z","timestamp":1790188270170,"version":"4.1.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Recanalization with tPA (tissue-type plasminogen activator) is the only pharmacological therapy available for patients with ischemic stroke. However, the percentage of patients who may receive this therapy is limited by the risk of hemorrhagic transformation (HT)\u2014the main complication of ischemic stroke. Our aim is to establish whether iron overload affects HT risk, to identify mechanisms that could help to select patients and to prevent this devastating complication.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>Mice fed with control or high-iron diet were subjected to thromboembolic stroke, with or without tPA therapy at different times after occlusion. Blood samples were collected for determination of malondialdehyde, matrix metalloproteinases, and fibronectin. Brain samples were collected 24 hours after occlusion to determine brain infarct and edema size, hemorrhage extension, IgG extravasation, and inflammatory and oxidative markers (neutrophil infiltration, 4-hydroxynonenal, and matrix metalloproteinase-9 staining).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>Despite an increased rate of recanalization, iron-overload mice showed less neuroprotection after tPA administration. Importantly, iron overload exacerbated the risk of HT after early tPA administration, accelerated ischemia-induced serum matrix metalloproteinase-9 increase, and enhanced basal serum lipid peroxidation. High iron increased brain lipid peroxidation at most times and neutrophil infiltration at the latest time studied.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our data showing that iron overload increases the death of the compromised tissues, accelerates the time of tPA-induced reperfusion, and exacerbates the risk of HT may have relevant clinical implications for a safer thrombolysis. Patients with stroke with iron overload might be at high risk of HT after fibrinolysis, and, therefore, clinical studies must be performed to confirm our results.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.118.021540","type":"journal-article","created":{"date-parts":[[2018,7,17]],"date-time":"2018-07-17T09:04:35Z","timestamp":1531818275000},"page":"2163-2172","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Iron Overload Exacerbates the Risk of Hemorrhagic Transformation After tPA (Tissue-Type Plasminogen Activator) Administration in Thromboembolic Stroke Mice"],"prefix":"10.1161","volume":"49","author":[{"given":"Isaac","family":"Garc\u00eda-Y\u00e9benes","sequence":"first","affiliation":[{"name":"From the Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Unidad de Investigaci\u00f3n Neurovascular, Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Universidad Complutense de Madrid, Spain (I.G.-Y., A.G.-C., C.P.-M., D.F.-L., M.A.M., I.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Garc\u00eda-Culebras","sequence":"additional","affiliation":[{"name":"From the Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Unidad de Investigaci\u00f3n Neurovascular, Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Universidad Complutense de Madrid, Spain (I.G.-Y., A.G.-C., C.P.-M., D.F.-L., M.A.M., I.L.)"},{"name":"Instituto de Investigaci\u00f3n Hospital 12 de Octubre (i+12), Madrid, Spain (A.G.-C., C.P.-M., M.A.M., I.L., J.D.-G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Pe\u00f1a-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"From the Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Unidad de Investigaci\u00f3n Neurovascular, Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Universidad Complutense de Madrid, Spain (I.G.-Y., A.G.-C., C.P.-M., D.F.-L., M.A.M., I.L.)"},{"name":"Instituto de Investigaci\u00f3n Hospital 12 de Octubre (i+12), Madrid, Spain (A.G.-C., C.P.-M., M.A.M., I.L., J.D.-G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fern\u00e1ndez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"From the Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Unidad de Investigaci\u00f3n Neurovascular, Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Universidad Complutense de Madrid, Spain (I.G.-Y., A.G.-C., C.P.-M., D.F.-L., M.A.M., I.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"D\u00edaz-Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, Hospital Universitario 12 de Octubre, Madrid, Spain (J.D.-G.)"},{"name":"Instituto de Investigaci\u00f3n Hospital 12 de Octubre (i+12), Madrid, Spain (A.G.-C., C.P.-M., M.A.M., I.L., J.D.-G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Negredo","sequence":"additional","affiliation":[{"name":"Departamento de Anatom\u00eda, Histolog\u00eda y Neurociencia, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, Spain (P.N., C.A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Avenda\u00f1o","sequence":"additional","affiliation":[{"name":"Departamento de Anatom\u00eda, Histolog\u00eda y Neurociencia, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, Spain (P.N., C.A.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Castellanos","sequence":"additional","affiliation":[{"name":"Servicio de Neurolog\u00eda, Complejo Hospitalario Universitario A Coru\u00f1a, Instituto de Investigaci\u00f3n Biom\u00e9dica A Coru\u00f1a, Spain (M.C.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Gasull","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Neurobiology Research Group, Fundaci\u00f3 Institut d\u2019Investigaci\u00f3 en Ci\u00e8ncies de la Salut Germans Trias i Pujol, Badalona, Spain (T.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"D\u00e1valos","sequence":"additional","affiliation":[{"name":"Departamento de Neurociencias, Unidad de Ictus, Hospital Universitari Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, Badalona, Spain (A.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda A.","family":"Moro","sequence":"additional","affiliation":[{"name":"From the Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Unidad de Investigaci\u00f3n Neurovascular, Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Universidad Complutense de Madrid, Spain (I.G.-Y., A.G.-C., C.P.-M., D.F.-L., M.A.M., I.L.)"},{"name":"Instituto de Investigaci\u00f3n Hospital 12 de Octubre (i+12), Madrid, Spain (A.G.-C., C.P.-M., M.A.M., I.L., J.D.-G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Lizasoain","sequence":"additional","affiliation":[{"name":"From the Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Unidad de Investigaci\u00f3n Neurovascular, Instituto Universitario de Investigaci\u00f3n en Neuroqu\u00edmica, Universidad Complutense de Madrid, Spain (I.G.-Y., A.G.-C., C.P.-M., D.F.-L., M.A.M., I.L.)"},{"name":"Instituto de Investigaci\u00f3n Hospital 12 de Octubre (i+12), Madrid, Spain (A.G.-C., C.P.-M., M.A.M., I.L., J.D.-G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199512143332401"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1995.03530130023023"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d1938"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00163-X"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70055-3"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1893"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi300752r"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-004-0445-9"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(96)00294-6"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000251798.25803.e0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.25.8.1543"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.8.1568"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-1331.2002.00472.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(02)03179-7"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00446.2002"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2012.09.014"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2011.03564.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.600452"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088812"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23682"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3468(90)90407-Z"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.023879"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.07.027"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44490"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(02)00160-0"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600140"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2004.04.001"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2008.04.002"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.3858\/emm.2011.43.2.020"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI41911"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301207"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.500868"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.002470"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.608257"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm926"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-203919"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2011.623808"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01275.2004"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1073634"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0907606"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000046764.57344.31"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1161\/hs1201.99512"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.002274"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00121"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.106.481556"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2012.10.013"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00114-9"}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.118.021540","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T14:46:16Z","timestamp":1715611576000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.118.021540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9]]},"references-count":47,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1161\/STROKEAHA.118.021540"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.118.021540","relation":{},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9]]},"assertion":[{"value":"2018-03-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}