{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T08:05:05Z","timestamp":1775894705594,"version":"3.50.1"},"posted":{"date-parts":[[2025,3,14]]},"group-title":"Neuroscience","reference-count":33,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 NS124846"],"award-info":[{"award-number":["R01 NS124846"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Previous data suggest that FOXO4 facilitates inflammation and oxidative stress in\n                  <jats:italic>non-brain tissues<\/jats:italic>\n                  under stress or disease conditions, indicating that blocking FOXO4 function may be neuroprotective in ischemia-reperfusion-induced brain injury. However, this possibility has not been tested in a cerebral ischemia-reperfusion condition. Here, we treated the FOXO4 knockout (KO) primary neuronal cultures with oxidative stress or oxygen-glucose deprivation (OGD) or subjected the KO mice to the transient middle cerebral artery occlusion (tMCAO). Our results showed that KO of FOXO4 reduced oxidative stress and OGD-induced neuronal death, attenuated tMCAO-caused infarct volume, improved animal survival, decreased neurological deficits, and enhanced functional recovery compared to the WT cells or mice. Immunohistochemical staining and Western blot analysis suggested decreased neuroinflammation in the KO brain. These data indicate that FOXO4 is a therapeutic target, and disrupting its activity promotes neuronal survival following ischemic stroke-induced brain injury.\n                <\/jats:p>","DOI":"10.1101\/2025.03.13.643180","type":"posted-content","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T11:35:15Z","timestamp":1741952115000},"source":"Crossref","is-referenced-by-count":0,"title":["Disrupting FOXO4 function confers neuroprotection against oxidative stress and ischemia-reperfusion-caused neuronal injury"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9222-6206","authenticated-orcid":false,"given":"Yasin","family":"Asadi","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Garrison Institute on Aging, and Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, Texas 79430-6592, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farhad","family":"Gorjipour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Garrison Institute on Aging, and Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, Texas 79430-6592, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rozenn K.","family":"Moundounga","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Garrison Institute on Aging, and Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, Texas 79430-6592, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abena","family":"Dwamena","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Garrison Institute on Aging, and Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, Texas 79430-6592, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augustina","family":"Potokiri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Garrison Institute on Aging, and Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, Texas 79430-6592, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin","family":"Gilstrap","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Garrison Institute on Aging, and Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, Texas 79430-6592, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Li","sequence":"additional","affiliation":[{"name":"Divisioin of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD 57069, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"McDowell","sequence":"additional","affiliation":[{"name":"Program in Biochemistry and Biocomputational Engineering, Lehigh University, Bethlehem, PA 18015, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0392-4458","authenticated-orcid":false,"given":"Hongmin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Garrison Institute on Aging, and Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, School of Medicine, Lubbock, Texas 79430-6592, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041100370001000_2025.03.13.643180v4.1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyac210"},{"key":"2026041100370001000_2025.03.13.643180v4.2","doi-asserted-by":"crossref","unstructured":"Baird AE , Jackson R , Jin W , editors. 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