{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T16:59:59Z","timestamp":1763398799265,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER\u2014Fundo Europeu de Desenvolvimento Regional through the COMPETE 2020\u2014Operational Programme for Competitiveness and Internationalization (POCI)","award":["UIDB\/4255\/2020","LA\/P\/0053\/2020","I F\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["UIDB\/4255\/2020","LA\/P\/0053\/2020","I F\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"Portuguese funds through FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia within CINTESIS, R&amp;D Unit","award":["UIDB\/4255\/2020","LA\/P\/0053\/2020","I F\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["UIDB\/4255\/2020","LA\/P\/0053\/2020","I F\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"the scope of the project \u201cRISE\u2013Associated Laboratory","award":["UIDB\/4255\/2020","LA\/P\/0053\/2020","I F\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["UIDB\/4255\/2020","LA\/P\/0053\/2020","I F\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"FCT and FEDER (European Union)","award":["UIDB\/4255\/2020","LA\/P\/0053\/2020","I F\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["UIDB\/4255\/2020","LA\/P\/0053\/2020","I F\/00092\/2014\/CP1255\/CT0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Hypoxia\u2013ischemia encephalopathy results from the interruption of oxygen delivery and blood flow to the brain. In the developing brain, it can lead to a brain injury, which is associated with high mortality rates and comorbidities. The hippocampus is one of the brain regions that may be affected by hypoxia\u2013ischemia with consequences on cognition. Unfortunately, clinically approved therapeutics are still scarce and limited. Therefore, in this study, we aimed to test three repurposed drugs with good pharmacological properties to evaluate if they can revert, or at least attenuate, the deleterious effects of hypoxia\u2013ischemia in an in vitro model. Edaravone, perampanel, and metformin are used for the treatment of stroke and amyotrophic lateral sclerosis, some forms of epileptic status, and diabetes type 2, respectively. Through cell viability assays, morphology analysis, and detection of reactive oxygen species (ROS) production, in two different cell lines (HT-22 and SH-SY5Y), we found that edaravone and low concentrations of perampanel are able to attenuate cell damage induced by hypoxia and oxygen-glucose deprivation. Metformin did not attenuate hypoxic-induced events, at least in the initial phase. Among these repurposed drugs, edaravone emerged as the most efficient in the attenuation of events induced by hypoxia\u2013ischemia, and the safest, since it did not exhibit significant cytotoxicity, even in high concentrations, and induced a decrease in ROS. Our results also reinforce the view that ROS and overexcitation play an important role in the pathophysiology of hypoxia\u2013ischemia brain injury.<\/jats:p>","DOI":"10.3390\/biomedicines10123043","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T04:31:16Z","timestamp":1669609876000},"page":"3043","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia\u2013Ischemia Encephalopathy: An In Vitro Study"],"prefix":"10.3390","volume":"10","author":[{"given":"Daniela","family":"Silva","sequence":"first","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]},{"given":"Ruben","family":"Rocha","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"Servi\u00e7o de Pediatria, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8231-1560","authenticated-orcid":false,"given":"Ana Salom\u00e9","family":"Correia","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8077-7247","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Mota","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]},{"given":"Maria Dulce","family":"Madeira","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2967-6990","authenticated-orcid":false,"given":"Armando","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Unit of Anatomy, Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"NeuroGen Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"709301","DOI":"10.3389\/fnsyn.2021.709301","article-title":"Current Therapies for Neonatal Hypoxic\u2013Ischaemic and Infection-Sensitised Hypoxic\u2013Ischaemic Brain Damage","volume":"13","author":"Tetorou","year":"2021","journal-title":"Front. 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