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Edaravone, a radical scavenger known for reducing oxidative stress, has shown neuroprotective effects in cerebral strokes, but its impact on cerebellar strokes remains unclear. This study investigates Edaravone\u2019s protective properties in organotypic slice cultures of rat cerebellum and hippocampus, employing an oxygen-glucose deprivation (OGD) model to simulate ischemic stroke. The hippocampus served as comparative structure due to its high hypoxia sensitivity. Our results confirmed effective hypoxic induction with increases in HIF-1\u03b1 and HIF-2\u03b1 expression. Edaravone significantly reduced lactate dehydrogenase (LDH) levels, indicating diminished cellular damage, with cerebellar tissues showing greater vulnerability. Additionally, Edaravone reduced reactive oxygen species (ROS) in both tissues, though its efficacy may be limited by higher oxidative stress in cerebellar cultures. Seahorse XF analysis revealed that Edaravone preserved mitochondrial respiration and tissue integrity in cerebellar and hippocampal slice cultures. However, Edaravone was more effective in preserving mitochondrial respiration in hippocampal slices, suggesting that OGD-induced damage is more severe in cerebellar tissue. In conclusion, Edaravone demonstrates significant cell protective effects in both cerebellar and hippocampal tissues under OGD conditions, preserving tissue integrity and enhancing mitochondrial function in a tissue-dependent manner. These findings suggest Edaravone as a promising therapeutic candidate for cerebellar stroke. Further in vivo studies are required to assess its full clinical potential.<\/jats:p>","DOI":"10.1007\/s12311-025-01804-3","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T05:19:12Z","timestamp":1739855952000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Differential Protective Effects of Edaravone in Cerebellar and Hippocampal Ischemic Injury Models"],"prefix":"10.1007","volume":"24","author":[{"given":"Jens","family":"Dickmei\u00df","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Henning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Stahlke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Theiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9717-4485","authenticated-orcid":false,"given":"Veronika","family":"Matschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,18]]},"reference":[{"key":"1804_CR1","doi-asserted-by":"crossref","unstructured":"Sarikaya H, Steinlin M. 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Semin Neurol. 2006;26:387\u201395.","journal-title":"Semin Neurol"}],"container-title":["The Cerebellum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12311-025-01804-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12311-025-01804-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12311-025-01804-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T09:35:47Z","timestamp":1741685747000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12311-025-01804-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,18]]},"references-count":58,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["1804"],"URL":"https:\/\/doi.org\/10.1007\/s12311-025-01804-3","relation":{},"ISSN":["1473-4230"],"issn-type":[{"value":"1473-4230","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,18]]},"assertion":[{"value":"11 February 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2025","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures were conducted under established standards of the German federal state of North Rhine Westphalia, in accordance with the European Communities Council Directive 2010\/63\/EU on the protection of animals used for scientific purposes. According to current German and European legislation, the removal of organs or cells from vertebrates for scientific purposes is not considered an animal experiment if the animals have not been subject to surgical interventions or invasive treatments prior to sacrifice. Thus, the euthanasia of rats for the removal of brain tissue does not require approval or permission from local or federal authorities.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Not applicable, as no human participants were involved in this research.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Human Ethics and Consent to Participate"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"49"}}