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Yet there remains a substantial proportion of infants who do not benefit or who will have significant disability despite therapeutic hypothermia. Novel investigational therapies that may confer additional neuroprotection by targeting known pathogenic mechanisms of hypoxic\u2013ischemic brain injury are under development. This review focuses on putative neuroprotective agents that have shown promise in animal models of HIE, and that have been translated to clinical studies in neonates with HIE. We include agents that have been studied both with and without concurrent therapeutic hypothermia. Our review therefore addresses not just neonatal HIE in high\u2010resource countries where therapeutic hypothermia is the standard of care, but also neonatal HIE in low\u2010 and middle\u2010income countries where therapeutic hypothermia has been shown to be ineffective, and where the greatest burden of HIE\u2010related morbidity and mortality exists.<\/jats:p>","DOI":"10.1111\/dmcn.16184","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T03:01:51Z","timestamp":1732071711000},"page":"591-599","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Neuroprotection for neonatal hypoxic\u2013ischemic encephalopathy: A\u00a0review of novel therapies evaluated in clinical studies"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5813-4779","authenticated-orcid":false,"given":"Natalie H.","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl C.","family":"Hawkins","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin V.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Coralie","family":"Cornet","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando F.","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne W.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2119660"},{"key":"e_1_2_9_3_1","first-page":"1","article-title":"Consensus definition and diagnostic criteria for neonatal encephalopathy\u2014study protocol for a real\u2010time modified delphi study","author":"Branagan A","year":"2024","journal-title":"Pediatr Res."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2023.08.037"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.earlhumdev.2010.05.010"},{"key":"e_1_2_9_6_1","unstructured":"SharrowD HugL LiuY LindtN NieW YouD.Levels and trends in child mortality \u2010 Report 2023 \u2010 Prepared by UN\u2010IGME [Internet].2024Mar [cited 2024 Apr 15]. 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