{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:21:42Z","timestamp":1777944102608,"version":"3.51.4"},"reference-count":43,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>Neuroprotection after ischemic stroke has been focused on targeting one pathway of the ischemic cascade. In this study, we have hypothesized that combination therapy with alpha-1 antitrypsin (A1AT) and a blocker of tumor necrosis factor (TNF\u03b1) could be beneficial in the acute phases after ischemia. Following a detailed safety assessment of the co-administration of both drugs, we tested their neuroprotective effect in a transient mouse model of proximal middle cerebral artery occlusion (MCAo) by evaluating infarct extension and functional outcomes. Anti-TNF\u03b1 (20\u2009mg\/kg) and A1AT were administered at different doses (ranging from 60\u2009mg\/kg to 700\u2009mg\/kg), as a single therapy during occlusion or at different time-points following reperfusion. Results showed that the administration of A1AT (60\u2009mg\/kg) in combination with anti-TNF\u03b1 (20\u2009mg\/kg) was safe and effective when given during occlusion by reducing infarct volume at 24\u2009h by 27% compared with the vehicle group (p\u2009=\u20090.0001). In conclusion, the synergy of the anti-apoptotic and anti-inflammatory properties of both drugs can reduce infarct volume in a stroke mouse model when given in the hyperacute phase. This approach shows promise as an early intervention strategy for stroke patients and underscores the potential of drug repurposing to develop new stroke treatments.<\/jats:p>","DOI":"10.1177\/0271678x251340234","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T04:36:13Z","timestamp":1747283773000},"page":"1993-2003","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Combination of alpha-1 antitrypsin (A1AT) and anti-TNF\u03b1 as a neuroprotective strategy in the early stages after ischemic stroke"],"prefix":"10.1177","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6596-8002","authenticated-orcid":false,"given":"Paula","family":"Garc\u00eda-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Neurovascular Research Laboratory, Vall d\u2019Hebron Institute of Research (VHIR), Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Ramiro","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Vall d\u2019Hebron Institute of Research (VHIR), Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0415-1135","authenticated-orcid":false,"given":"Alba","family":"Simats","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Vall d\u2019Hebron Institute of Research (VHIR), Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feifei","family":"Ma","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Vall d\u2019Hebron Institute of Research (VHIR), Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1082-3599","authenticated-orcid":false,"given":"Anna","family":"Rosell","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Vall d\u2019Hebron Institute of Research (VHIR), Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4845-2279","authenticated-orcid":false,"given":"Joan","family":"Montaner","sequence":"additional","affiliation":[{"name":"Neurovascular Research Laboratory, Vall d\u2019Hebron Institute of Research (VHIR), Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"},{"name":"Stroke Research Program, Institute of Biomedicine of Seville, IBiS\/Hospital Universitario Virgen del Roc\u00edo\/CSIC\/University of Seville &amp; 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