{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T11:16:01Z","timestamp":1775301361230,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T00:00:00Z","timestamp":1585612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/00255"],"award-info":[{"award-number":["PI18\/00255"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RD16\/0019\/0006"],"award-info":[{"award-number":["RD16\/0019\/0006"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2015-65586-R"],"award-info":[{"award-number":["SAF2015-65586-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["CTQ2016-78205-P"],"award-info":[{"award-number":["CTQ2016-78205-P"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["CTQ2016-81797-REDC"],"award-info":[{"award-number":["CTQ2016-81797-REDC"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Nitrones have a well-recognized capacity as spin-traps and are considered powerful free radical scavengers, which are two important issues in hypoxia-induced oxidative stress and cell death in brain ischemia. Consequently, nitrones have been proposed as therapeutic agents in acute ischemic stroke (AIS). In this paper, we update the biological and pharmacological characterization of ISQ-201, a previously identified cholesteronitrone hybrid with antioxidant and neuroprotective activity. This study characterizes ISQ-201 as a neuroprotective agent against the hypoxia-induced ischemic injury. Transitory four-vessel occlusion and middle cerebral artery occlusion (tMCAO) were used to induce cerebral ischemia. Functional outcomes were determined using neurofunctional tests. Infarct area, neuronal death, and apoptosis induction were evaluated. In addition, ISQ-201 reactivity towards free radicals was studied in a theoretical model. ISQ-201 significantly decreased the ischemia-induced neuronal death and apoptosis, in a dose-dependent manner, showing its therapeutic effect when administered up until 6 h after post-ischemic reperfusion onset, effects that remained after 3 months from the ischemic episode. Furthermore, ISQ-201 significantly reduced infarct volume, leading to recovery of the motor function in the tMCAO model. Finally, the theoretical study confirmed the reactivity of ISQ-201 towards hydroxyl radicals. The results reported here prompted us to suggest ISQ-201 as a promising candidate for the treatment of AIS.<\/jats:p>","DOI":"10.3390\/antiox9040291","type":"journal-article","created":{"date-parts":[[2020,3,31]],"date-time":"2020-03-31T13:27:19Z","timestamp":1585661239000},"page":"291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Characterization of a CholesteroNitrone (ISQ-201), a Novel Drug Candidate for the Treatment of Ischemic Stroke"],"prefix":"10.3390","volume":"9","author":[{"given":"Emma","family":"Mart\u00ednez-Alonso","sequence":"first","affiliation":[{"name":"Department of Research, IRYCIS, Hospital Ram\u00f3n y Cajal, Ctra. Colmenar km 9.1, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6408-2012","authenticated-orcid":false,"given":"Alejandro","family":"Escobar-Peso","sequence":"additional","affiliation":[{"name":"Department of Research, IRYCIS, Hospital Ram\u00f3n y Cajal, Ctra. Colmenar km 9.1, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria I.","family":"Ayuso","sequence":"additional","affiliation":[{"name":"Neurovascular Research Group, Institute of Biomedicine of Seville, IBiS, Hospital Universitario Virgen del Roc\u00edo, Av. Manuel Siurot s\/n, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6357-105X","authenticated-orcid":false,"given":"Rafael","family":"Gonzalo-Gobernado","sequence":"additional","affiliation":[{"name":"Neurovascular Research Group, Institute of Biomedicine of Seville, IBiS, Hospital Universitario Virgen del Roc\u00edo, Av. Manuel Siurot s\/n, 41013 Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mourad","family":"Chioua","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry (IQOG, CSIC), C\/Juan de la Cierva 3, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan J.","family":"Montoya","sequence":"additional","affiliation":[{"name":"Isquaemia Biotech SL, Scientific Technological Park, C\/Astr\u00f3noma Cecilia Payne s\/n, 14014 C\u00f3rdoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Montaner","sequence":"additional","affiliation":[{"name":"Neurovascular Research Group, Institute of Biomedicine of Seville, IBiS, Hospital Universitario Virgen del Roc\u00edo, Av. Manuel Siurot s\/n, 41013 Seville, Spain"},{"name":"Neurovascular Research Laboratory, Institut de Recerca Vall d\u2019Hebron, Aut\u00f2noma University of Barcelona, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0186-9774","authenticated-orcid":false,"given":"Israel","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica I y Centro de Innovaci\u00f3n en Qu\u00edmica Avanzada (ORFEO-CINQA), Complutense University of Madrid, Av. Complutense s\/n, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9","family":"Marco-Contelles","sequence":"additional","affiliation":[{"name":"Laboratory of Medicinal Chemistry (IQOG, CSIC), C\/Juan de la Cierva 3, 28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Alc\u00e1zar","sequence":"additional","affiliation":[{"name":"Department of Research, IRYCIS, Hospital Ram\u00f3n y Cajal, Ctra. Colmenar km 9.1, 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,31]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2016). 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