{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:32:09Z","timestamp":1785216729441,"version":"3.55.0"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Brain, Behavior, and Immunity"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.bbi.2020.12.027","type":"journal-article","created":{"date-parts":[[2021,1,2]],"date-time":"2021-01-02T11:14:36Z","timestamp":1609586076000},"page":"288-298","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":29,"special_numbering":"C","title":["Elastase inhibitor agaphelin protects from acute ischemic stroke in mice by reducing thrombosis, blood\u2013brain barrier damage, and inflammation"],"prefix":"10.1016","volume":"93","author":[{"given":"Jonas","family":"Leinweber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella M.","family":"Mizurini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo M.B.","family":"Francischetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fleischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk M.","family":"Hermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kleinschnitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"Langhauser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bbi.2020.12.027_b0005","doi-asserted-by":"crossref","first-page":"381","DOI":"10.4049\/jimmunol.1200409","article-title":"Neutrophil cerebrovascular transmigration triggers rapid neurotoxicity through release of proteases associated with decondensed DNA","volume":"189","author":"Allen","year":"2012","journal-title":"J. Immunol."},{"key":"10.1016\/j.bbi.2020.12.027_b0010","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1054\/jocn.2001.1031","article-title":"Ischaemic brain oedema","volume":"9","author":"Ayata","year":"2002","journal-title":"J. Clin. Neurosci."},{"key":"10.1016\/j.bbi.2020.12.027_b0015","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1161\/01.STR.17.3.472","article-title":"Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination","volume":"17","author":"Bederson","year":"1986","journal-title":"Stroke"},{"key":"10.1016\/j.bbi.2020.12.027_b0020","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/2040-7378-1-8","article-title":"Rodent models of focal cerebral ischemia: procedural pitfalls and translational problems","volume":"1","author":"Braeuninger","year":"2009","journal-title":"Experimental Transl. Stroke Med."},{"key":"10.1016\/j.bbi.2020.12.027_b0025","first-page":"H1947","article-title":"Protease inhibition attenuates microvascular dysfunction in postischemic skeletal muscle","volume":"271","author":"Carden","year":"1996","journal-title":"Am. J. Physiol."},{"key":"10.1016\/j.bbi.2020.12.027_b0030","first-page":"317","article-title":"Evaluation of granulocyte elastase as a sensitive diagnostic parameter of inflammation in first ischemic stroke","volume":"44","author":"Cojocaru","year":"2006","journal-title":"Rom. J. Intern. Med."},{"key":"10.1016\/j.bbi.2020.12.027_b0035","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1161\/STROKEAHA.109.557447","article-title":"When recanalization does not improve clinical outcomes","volume":"40","author":"Coutts","year":"2009","journal-title":"Stroke"},{"key":"10.1016\/j.bbi.2020.12.027_b0040","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1161\/STROKEAHA.115.011238","article-title":"Thromboinflammation in stroke brain damage","volume":"47","author":"De Meyer","year":"2016","journal-title":"Stroke"},{"key":"10.1016\/j.bbi.2020.12.027_b0045","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1161\/01.STR.0000138023.60272.9e","article-title":"Targets for vascular protection after acute ischemic stroke","volume":"35","author":"Fagan","year":"2004","journal-title":"Stroke"},{"key":"10.1016\/j.bbi.2020.12.027_b0050","doi-asserted-by":"crossref","DOI":"10.1016\/j.imbio.2020.151937","article-title":"Agaphelin modulates the activation of human bronchial epithelial cells induced by lipopolysaccharide and IL-4","volume":"225","author":"Favarin","year":"2020","journal-title":"Immunobiology"},{"key":"10.1016\/j.bbi.2020.12.027_b0055","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1083\/jcb.200606027","article-title":"Novel cell death program leads to neutrophil extracellular traps","volume":"176","author":"Fuchs","year":"2007","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.bbi.2020.12.027_b0060","doi-asserted-by":"crossref","first-page":"15880","DOI":"10.1073\/pnas.1005743107","article-title":"Extracellular DNA traps promote thrombosis","volume":"107","author":"Fuchs","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.bbi.2020.12.027_b0065","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1183\/09031936.00212114","article-title":"Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis","volume":"46","author":"Garratt","year":"2015","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.bbi.2020.12.027_b0070","first-page":"543","article-title":"ERK inhibition with PD184161 mitigates brain damage in a mouse model of stroke","volume":"121","author":"Gladbach","year":"2014","journal-title":"J. Neural. Transm. (Vienna)"},{"key":"10.1016\/j.bbi.2020.12.027_b0075","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.brainres.2013.04.010","article-title":"Inhibitory effects of p38 inhibitor against mitochondrial dysfunction in the early brain injury after subarachnoid hemorrhage in mice","volume":"1517","author":"Huang","year":"2013","journal-title":"Brain Res."},{"key":"10.1016\/j.bbi.2020.12.027_b0080","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/hr.2010.58","article-title":"Neutrophil elastase inhibitor prevents ischemic brain damage via reduction of vasogenic edema","volume":"33","author":"Ikegame","year":"2010","journal-title":"Hypertens. Res."},{"key":"10.1016\/j.bbi.2020.12.027_b0085","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.brainresbull.2011.09.021","article-title":"Polydatin modulates inflammation by decreasing NF-kappaB activation and oxidative stress by increasing Gli1, Ptch1, SOD1 expression and ameliorates blood-brain barrier permeability for its neuroprotective effect in pMCAO rat brain","volume":"87","author":"Ji","year":"2012","journal-title":"Brain Res. Bull."},{"key":"10.1016\/j.bbi.2020.12.027_b0090","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1006\/cimm.1995.1183","article-title":"Suppressive effect of a neutrophil elastase inhibitor on the development of collagen-induced arthritis","volume":"165","author":"Kakimoto","year":"1995","journal-title":"Cell. Immunol."},{"key":"10.1016\/j.bbi.2020.12.027_b0095","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1164\/ajrccm.161.6.9904047","article-title":"Delayed neutrophil elastase inhibition prevents subsequent progression of acute lung injury induced by endotoxin inhalation in hamsters","volume":"161","author":"Kawabata","year":"2000","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.bbi.2020.12.027_b0100","doi-asserted-by":"crossref","unstructured":"Kleinschnitz, C., Grund, H., Wingler, K., Armitage, M.E., Jones, E., Mittal, M., Barit, D., Schwarz, T., Geis, C., Kraft, P., Barthel, K., Schuhmann, M.K., Herrmann, A.M., Meuth, S.G., Stoll, G., Meurer, S., Schrewe, A., Becker, L., Gailus-Durner, V., Fuchs, H., Klopstock, T., de Angelis, M.H., Jandeleit-Dahm, K., Shah, A.M., Weissmann, N., Schmidt, H.H., 2010. Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration. PLoS Biol 8.","DOI":"10.1371\/journal.pbio.1000479"},{"key":"10.1016\/j.bbi.2020.12.027_b0105","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1084\/jem.20052458","article-title":"Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis","volume":"203","author":"Kleinschnitz","year":"2006","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.bbi.2020.12.027_b0110","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1038\/jcbfm.2012.108","article-title":"Next-generation antithrombotics in ischemic stroke: preclinical perspective on 'bleeding-free antithrombosis'","volume":"32","author":"Kraft","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"10.1016\/j.bbi.2020.12.027_b0115","doi-asserted-by":"crossref","first-page":"4082","DOI":"10.1182\/blood-2012-06-440057","article-title":"Kininogen deficiency protects from ischemic neurodegeneration in mice by reducing thrombosis, blood-brain barrier damage, and inflammation","volume":"120","author":"Langhauser","year":"2012","journal-title":"Blood"},{"key":"10.1016\/j.bbi.2020.12.027_b0120","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.transproceed.2014.10.045","article-title":"Erythropoietin pretreatment exerts anti-inflammatory effects in hepatic ischemia\/reperfusion-injured rats via suppression of the TLR2\/NF-kappaB pathway","volume":"47","author":"Liu","year":"2015","journal-title":"Transplant Proc"},{"key":"10.1016\/j.bbi.2020.12.027_b0125","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1097\/WCO.0b013e328352ede6","article-title":"Immune mechanisms of stroke","volume":"25","author":"Magnus","year":"2012","journal-title":"Curr. Opin. Neurol."},{"key":"10.1016\/j.bbi.2020.12.027_b0130","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1182\/blood-2013-10-463646","article-title":"Thrombosis: tangled up in NETs","volume":"123","author":"Martinod","year":"2014","journal-title":"Blood"},{"key":"10.1016\/j.bbi.2020.12.027_b0135","doi-asserted-by":"crossref","first-page":"5341","DOI":"10.1073\/pnas.92.12.5341","article-title":"Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human beta-amyloid precursor protein","volume":"92","author":"Moran","year":"1995","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.bbi.2020.12.027_b0140","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00401-014-1355-2","article-title":"Very-late-antigen-4 (VLA-4)-mediated brain invasion by neutrophils leads to interactions with microglia, increased ischemic injury and impaired behavior in experimental stroke","volume":"129","author":"Neumann","year":"2015","journal-title":"Acta Neuropathol."},{"key":"10.1016\/j.bbi.2020.12.027_b0145","doi-asserted-by":"crossref","first-page":"4115","DOI":"10.1113\/jphysiol.2011.212886","article-title":"Ischaemic stroke: a thrombo-inflammatory disease?","volume":"589","author":"Nieswandt","year":"2011","journal-title":"J. Physiol."},{"key":"10.1016\/j.bbi.2020.12.027_b0150","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1038\/jcbfm.2008.60","article-title":"Role of the p38 mitogen-activated protein kinase\/cytosolic phospholipase A2 signaling pathway in blood-brain barrier disruption after focal cerebral ischemia and reperfusion","volume":"28","author":"Nito","year":"2008","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"10.1016\/j.bbi.2020.12.027_b0155","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nri1841","article-title":"Neutrophil serine proteases: specific regulators of inflammation","volume":"6","author":"Pham","year":"2006","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.bbi.2020.12.027_b0160","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.brainres.2012.02.003","article-title":"Luteolin downregulates TLR4, TLR5, NF-kappaB and p-p38MAPK expression, upregulates the p-ERK expression, and protects rat brains against focal ischemia","volume":"1448","author":"Qiao","year":"2012","journal-title":"Brain Res."},{"key":"10.1016\/j.bbi.2020.12.027_b0165","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1146\/annurev.ento.48.060402.102812","article-title":"Role of arthropod saliva in blood feeding: sialome and post-sialome perspectives","volume":"48","author":"Ribeiro","year":"2003","journal-title":"Annu. Rev. Entomol."},{"key":"10.1016\/j.bbi.2020.12.027_b0170","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1161\/STROKEAHA.107.500868","article-title":"MMP-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type IV collagen degradation during hemorrhagic transformation after human ischemic stroke","volume":"39","author":"Rosell","year":"2008","journal-title":"Stroke"},{"key":"10.1016\/j.bbi.2020.12.027_b0175","doi-asserted-by":"crossref","first-page":"11636","DOI":"10.1074\/jbc.272.17.11636","article-title":"Human neutrophil elastase proteolytically activates the platelet integrin alphaIIbbeta3 through cleavage of the carboxyl terminus of the alphaIIb subunit heavy chain. Involvement in the potentiation of platelet aggregation","volume":"272","author":"Si-Tahar","year":"1997","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bbi.2020.12.027_b0180","doi-asserted-by":"crossref","first-page":"3555","DOI":"10.1182\/blood-2008-04-144758","article-title":"Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment","volume":"112","author":"Stoll","year":"2008","journal-title":"Blood"},{"key":"10.1016\/j.bbi.2020.12.027_b0185","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1749-6632.2010.05730.x","article-title":"Combating innate inflammation: a new paradigm for acute treatment of stroke?","volume":"1207","author":"Stoll","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.bbi.2020.12.027_b0190","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.nbd.2009.04.006","article-title":"Neutrophil elastase and neurovascular injury following focal stroke and reperfusion","volume":"35","author":"Stowe","year":"2009","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.bbi.2020.12.027_b0195","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1084\/jem.20112322","article-title":"Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo","volume":"209","author":"von Bruhl","year":"2012","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.bbi.2020.12.027_b0200","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1004338","article-title":"Plasmodium falciparum infection induces expression of a mosquito salivary protein (Agaphelin) that targets neutrophil function and inhibits thrombosis without impairing hemostasis","volume":"10","author":"Waisberg","year":"2014","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.bbi.2020.12.027_b0205","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.bbamem.2008.10.022","article-title":"The blood-brain barrier in brain homeostasis and neurological diseases","volume":"1788","author":"Weiss","year":"2009","journal-title":"Biochim. Biophys. Acta"}],"container-title":["Brain, Behavior, and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0889159120324855?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0889159120324855?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:09:56Z","timestamp":1760170196000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0889159120324855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":41,"alternative-id":["S0889159120324855"],"URL":"https:\/\/doi.org\/10.1016\/j.bbi.2020.12.027","relation":{},"ISSN":["0889-1591"],"issn-type":[{"value":"0889-1591","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Elastase inhibitor agaphelin protects from acute ischemic stroke in mice by reducing thrombosis, blood\u2013brain barrier damage, and inflammation","name":"articletitle","label":"Article Title"},{"value":"Brain, Behavior, and Immunity","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbi.2020.12.027","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}