{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:36:02Z","timestamp":1740137762856,"version":"3.37.3"},"reference-count":47,"publisher":"Georg Thieme Verlag KG","issue":"08","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Ministerio de Econom\u00eda y Competitividad, Instituto de Salud Carlos III","award":["FIS PI15\/01807"],"award-info":[{"award-number":["FIS PI15\/01807"]}]},{"name":"Ministerio de Econom\u00eda y Competitividad, Instituto de Salud Carlos III","award":["PI19\/00065"],"award-info":[{"award-number":["PI19\/00065"]}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Spanish Society of Thrombosis and Haemostasis"},{"name":"Navarra Government"},{"name":"Virto Group"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:p>\n            Background\u2003Intracranial hemorrhage (ICH) is one of the major devastating complications of anticoagulation. Matrix metalloproteinase (MMP) inhibition has been proposed as a novel pharmacological approach for ICH treatment.<\/jats:p><jats:p>\n            Objectives\u2003We evaluated the effects of CM-352 (MMP-fibrinolysis inhibitor) in an experimental ICH model associated with oral anticoagulants as compared with clinically used prothrombin complex concentrate (PCC).<\/jats:p><jats:p>\n            Methods\u2003ICH was induced by collagenase injection into the striatum of wild type (C57BL\/6J) anticoagulated mice (warfarin or rivaroxaban) and Mmp10\u2009\u2212\/\u2212 mice. Hematoma volume and neurological deficits were measured 24\u2009hours later by diaminobenzidine staining and different behavioral tests. Circulating plasminogen activator inhibitor-1 (PAI-1) activity and interleukin-6 (IL-6) were measured in plasma samples and local inflammation was assessed by neutrophil infiltration. Finally, fibrinolytic effects of MMP-10 and rivaroxaban were evaluated by thromboelastometry and thrombin-activatable fibrinolysis inhibitor (TAFI) activation assays.<\/jats:p><jats:p>\n            Results\u2003Only PCC reduced hemorrhage volume and improved functional outcome in warfarin-ICH, but both PCC and CM-352 treatments diminished hemorrhage volume (46%, p\u2009&lt;\u20090.01 and 64%, p\u2009&lt;\u20090.001, respectively) and ameliorated functional outcome in rivaroxaban-ICH. We further demonstrated that CM-352, but not PCC, decreased neutrophil infiltration in the hemorrhage area at 24\u2009hours. The effect of CM-352 could be related to MMP-10 inhibition since Mmp10\u2009\u2212\/\u2212 mice showed lower hemorrhage volume, better neurological score, reduced IL-6 levels and neutrophil infiltration, and increased PAI-1 after experimental ICH. Finally, we found that CM-352 reduced MMP-10 and rivaroxaban-related fibrinolytic effects in thromboelastometry and TAFI activation.<\/jats:p><jats:p>\n            Conclusion\u2003CM-352 treatment, by diminishing MMPs and rivaroxaban-associated fibrinolytic effects, might be a novel antihemorrhagic strategy for rivaroxaban-associated ICH.<\/jats:p>","DOI":"10.1055\/a-1759-9962","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:10:51Z","timestamp":1643933451000},"page":"1314-1325","source":"Crossref","is-referenced-by-count":1,"title":["CM-352 Efficacy in a Mouse Model of Anticoagulant-Associated Intracranial Hemorrhage"],"prefix":"10.1055","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-5501","authenticated-orcid":false,"given":"Manuel","family":"Navarro-Oviedo","sequence":"additional","affiliation":[{"name":"Laboratory of Atherothrombosis, CIMA Universidad de Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, IdisNA, Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1807-4297","authenticated-orcid":false,"given":"Juan","family":"Marta-Enguita","sequence":"additional","affiliation":[{"name":"Laboratory of Atherothrombosis, CIMA Universidad de Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, IdisNA, Pamplona, Spain"},{"name":"Neurology Department, Complejo Hospitalario de Navarra, IdisNA, Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0616-9600","authenticated-orcid":false,"given":"Carmen","family":"Roncal","sequence":"additional","affiliation":[{"name":"Laboratory of Atherothrombosis, CIMA Universidad de Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, IdisNA, Pamplona, Spain"},{"name":"Neurology Department, Complejo Hospitalario de Navarra, IdisNA, Pamplona, Spain"},{"name":"CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2094-264X","authenticated-orcid":false,"given":"Jose A.","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratory of Atherothrombosis, CIMA Universidad de Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, IdisNA, Pamplona, Spain"},{"name":"Neurology Department, Complejo Hospitalario de Navarra, IdisNA, Pamplona, Spain"},{"name":"CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Zandio","sequence":"additional","affiliation":[{"name":"Neurology Department, Complejo Hospitalario de Navarra, IdisNA, Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram\u00f3n","family":"Lecumberri","sequence":"additional","affiliation":[{"name":"CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Spain"},{"name":"Haematology Department, Cl\u00ednica Universidad de Navarra, Pamplona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3154-4484","authenticated-orcid":false,"given":"Jose","family":"Hermida","sequence":"additional","affiliation":[{"name":"Laboratory of Atherothrombosis, CIMA Universidad de Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, IdisNA, Pamplona, Spain"},{"name":"Neurology Department, Complejo Hospitalario de Navarra, IdisNA, Pamplona, Spain"},{"name":"CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1941-7255","authenticated-orcid":false,"given":"Julen","family":"Oyarzabal","sequence":"additional","affiliation":[{"name":"Small Molecules Platform, CIMA Universidad de Navarra, Instituto de Investigaci\u00f3n Sanitaria de Navarra, IdisNA, Pamplona, 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thrombosis","volume":"177","author":"N H Schultz","year":"2019","journal-title":"Thromb Res"},{"issue":"01","key":"ref30","doi-asserted-by":"crossref","first-page":"10329","DOI":"10.1038\/s41598-020-67250-9","article-title":"Circulating TIMP-1 is associated with hematoma volume in patients with spontaneous intracranial hemorrhage","volume":"10","author":"M Navarro-Oviedo","year":"2020","journal-title":"Sci Rep"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-021-07192-0","article-title":"Efficacy and safety of the fixed-dose versus variable-dose of 4-PCC for vitamin K antagonist reversal: a comprehensive systematic review and meta-analysis","author":"K Mohammadi","year":"2021","journal-title":"Cardiovasc Drugs Ther"},{"issue":"04","key":"ref32","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1177\/2396987319849763","article-title":"European Stroke Organisation guideline on reversal of oral anticoagulants in acute intracerebral 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Tanaka","year":"2014","journal-title":"J Intensive Care"},{"issue":"07","key":"ref36","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1182\/blood-2011-03-343046","article-title":"Increasing concentrations of prothrombin complex concentrate induce disseminated intravascular coagulation in a pig model of coagulopathy with blunt liver injury","volume":"118","author":"O Grottke","year":"2011","journal-title":"Blood"},{"issue":"01","key":"ref37","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s13054-019-2492-8","article-title":"Reversal of oral anticoagulation in patients with acute intracerebral hemorrhage","volume":"23","author":"J B Kuramatsu","year":"2019","journal-title":"Crit Care"},{"issue":"21","key":"ref38","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1161\/CIRCULATIONAHA.120.045769","article-title":"Factor Xa inhibitor-related intracranial hemorrhage: results from a multicenter, observational cohort receiving prothrombin complex 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Tai","year":"2010","journal-title":"J Pineal Res"},{"issue":"01","key":"ref45","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1158\/0008-5472.CAN-06-2448","article-title":"Extracellular matrix metalloproteinase inducer up-regulates the urokinase-type plasminogen activator system promoting tumor cell invasion","volume":"67","author":"C Quemener","year":"2007","journal-title":"Cancer Res"},{"issue":"40","key":"ref46","doi-asserted-by":"crossref","first-page":"10281","DOI":"10.1523\/JNEUROSCI.2806-06.2006","article-title":"Combination of thrombin and matrix metalloproteinase-9 exacerbates neurotoxicity in cell culture and intracerebral hemorrhage in mice","volume":"26","author":"M Xue","year":"2006","journal-title":"J Neurosci"},{"issue":"01","key":"ref47","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.1460-9568.2004.03829.x","article-title":"Matrix metalloproteinase (MMP)-12 expression has a negative impact on sensorimotor function following intracerebral 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