{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T20:26:44Z","timestamp":1777321604366,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Neonatal hypoxic\u2013ischemic encephalopathy (HIE) is a severe neurological injury during infancy, often resulting in long\u2010term cognitive deficits. This study aimed to investigate the neuroprotective effects of Edaravone (EDA), a free radical scavenger, and elucidate the potential role of brain\u2010derived neurotrophic factor (BDNF) in mediating these effects in neonatal HIE rats. Using the Rice\u2010Vannucci model, HIE was induced in neonatal rats, followed by immediate administration of EDA after the hypoxic\u2013ischemic insult. To examine the role of BDNF, a separate group of rats received intrahippocampal injections of a lentiviral vector for BDNF knockdown prior to the induction of HIE and subsequent EDA treatment. Neuronal survival and apoptosis in the hippocampal region were assessed by immunofluorescence and TUNEL staining, respectively. BDNF expression levels in the hippocampus were analysed using enzyme\u2010linked immunosorbent assay (ELISA). Cognitive function was evaluated using the Morris water maze (MWM) and Y maze tests. Results demonstrated that EDA significantly reduced hippocampal neuronal apoptosis and death, increased neuronal survival, and enhanced BDNF expression compared to the control group. However, the therapeutic effects of EDA were mitigated in the BDNF knockdown group, indicating a crucial role of BDNF in mediating the neuroprotective effects of EDA. Behavioural testing confirmed that EDA treatment significantly improved spatial learning and memory abilities in HIE rats, but these improvements were not observed in rats with BDNF knockdown. In conclusion, our study suggests that EDA treatment mitigates hippocampal neuronal death and improves cognitive dysfunction in HIE rats primarily by upregulating BDNF expression. These findings provide experimental support for the potential application of EDA in the treatment of HIE and highlight the essential role of BDNF in neuroprotection and cognitive recovery post\u2010HIE.<\/jats:p>","DOI":"10.1002\/jdn.10413","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T14:04:16Z","timestamp":1737381856000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Edaravone Mitigates Hippocampal Neuronal Death and Cognitive Dysfunction by Upregulating BDNF Expression in Neonatal Hypoxic\u2013Ischemic Rats"],"prefix":"10.1002","volume":"85","author":[{"given":"Rui","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Digestive and Nutrition, College of Clinical Medicine for Obstetrics &amp; Gynecology and Pediatrics Fujian Medical University  Fuzhou Fujian China"},{"name":"Fujian Children's Hospital (Fujian Branch of Shanghai children's Medical Center)  Fuzhou Fujian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongkai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Affiliated Fuzhou First Hospital of Fujian Medical University  Fuzhou Fujian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7880-2482","authenticated-orcid":false,"given":"Yijun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Digestive and Nutrition, College of Clinical Medicine for Obstetrics &amp; 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