{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:19:51Z","timestamp":1792804791969,"version":"4.5.0"},"reference-count":67,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Stem Cell Network","id":[{"id":"https:\/\/ror.org\/03se16w85","id-type":"ROR","asserted-by":"crossref"}]},{"name":"CFREF\u2014Medicine by Design"},{"name":"CIHR","id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NSERC","id":[{"id":"https:\/\/ror.org\/01h531d29","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Heart and Stroke Foundation","id":[{"id":"https:\/\/ror.org\/00qbpyp73","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Stroke results in neuronal cell death, which causes long-term disabilities in adults. Treatment options are limited and rely on a narrow window of opportunity. Apoptosis inhibitors demonstrate efficacy in improving neuronal cell survival in animal models of stroke. However, many inhibitors non-specifically target apoptosis pathways and high doses are needed for treatment. We explored the use of a novel caspase-3\/7 inhibitor, New World Laboratories (NWL) 283, with a lower IC50 than current caspase-3\/7 inhibitors. We performed in vitro and in vivo assays to determine the efficacy of NWL283 in modulating cell death in a preclinical model of stroke. In vitro and in vivo assays show that NWL283 enhances cell survival of neural precursor cells. Delivery of NWL283 following stroke enhances endogenous NPC migration and leads to increased neurogenesis in the stroke-injured cortex. Furthermore, acute NWL283 administration is neuroprotective at the stroke injury site, decreasing neuronal cell death and reducing microglia activation. Coincident with NWL283 delivery for 8 days, stroke-injured mice exhibited improved functional outcomes that persisted following cessation of the drug. Therefore, we propose that NWL283 is a promising therapeutic warranting further investigation to enhance stroke recovery.<\/jats:p>","DOI":"10.3390\/ijms25031786","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T08:44:08Z","timestamp":1706777048000},"page":"1786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Inhibition of Apoptosis in a Model of Ischemic Stroke Leads to Enhanced Cell Survival, Endogenous Neural Precursor Cell Activation and Improved Functional Outcomes"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8105-4486","authenticated-orcid":false,"given":"Rehnuma","family":"Islam","sequence":"first","affiliation":[{"name":"Institute of Medical Science, University of Toronto, 1 King\u2019s College Circle, Toronto, ON M5S 3E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Eric","family":"Ahlfors","sequence":"additional","affiliation":[{"name":"New World Laboratories, 275 Boul. Armand-Frappier, Laval, QC H7V 4A7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricky","family":"Siu","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Toronto, 149 College Street, Toronto, ON M5T 1P5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humna","family":"Noman","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Toronto, 1 King\u2019s College Circle, Toronto, ON M5S 3E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roya","family":"Akbary","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Toronto, 149 College Street, Toronto, ON M5T 1P5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindi M.","family":"Morshead","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Toronto, 1 King\u2019s College Circle, Toronto, ON M5S 3E1, Canada"},{"name":"Department of Surgery, University of Toronto, 149 College Street, Toronto, ON M5T 1P5, Canada"},{"name":"Institute of Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON M5S 3G9, Canada"},{"name":"Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON M5S 3E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1007\/s10072-017-2938-1","article-title":"Pathogenic Mechanisms Following Ischemic Stroke","volume":"38","author":"Khoshnam","year":"2017","journal-title":"Neurol. 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