000258240 001__ 258240 000258240 005__ 20231004134645.0 000258240 0247_ $$2doi$$a10.1038/s41598-023-36653-9 000258240 0247_ $$2pmid$$apmid:37301929 000258240 0247_ $$2pmc$$apmc:PMC10257179 000258240 0247_ $$2altmetric$$aaltmetric:149871342 000258240 037__ $$aDZNE-2023-00586 000258240 041__ $$aEnglish 000258240 082__ $$a600 000258240 1001_ $$0P:(DE-2719)9000732$$aSabir, Hemmen$$b0$$eFirst author$$udzne 000258240 245__ $$aComparing the efficacy in reducing brain injury of different neuroprotective agents following neonatal hypoxia-ischemia in newborn rats: a multi-drug randomized controlled screening trial. 000258240 260__ $$a[London]$$bMacmillan Publishers Limited, part of Springer Nature$$c2023 000258240 3367_ $$2DRIVER$$aarticle 000258240 3367_ $$2DataCite$$aOutput Types/Journal article 000258240 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1688477009_1577 000258240 3367_ $$2BibTeX$$aARTICLE 000258240 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000258240 3367_ $$00$$2EndNote$$aJournal Article 000258240 520__ $$aIntrapartum hypoxia-ischemia leading to neonatal encephalopathy (NE) results in significant neonatal mortality and morbidity worldwide, with > 85% of cases occurring in low- and middle-income countries (LMIC). Therapeutic hypothermia (HT) is currently the only available safe and effective treatment of HIE in high-income countries (HIC); however, it has shown limited safety or efficacy in LMIC. Therefore, other therapies are urgently required. We aimed to compare the treatment effects of putative neuroprotective drug candidates following neonatal hypoxic-ischemic (HI) brain injury in an established P7 rat Vannucci model. We conducted the first multi-drug randomized controlled preclinical screening trial, investigating 25 potential therapeutic agents using a standardized experimental setting in which P7 rat pups were exposed to unilateral HI brain injury. The brains were analysed for unilateral hemispheric brain area loss after 7 days survival. Twenty animal experiments were performed. Eight of the 25 therapeutic agents significantly reduced brain area loss with the strongest treatment effect for Caffeine, Sonic Hedgehog Agonist (SAG) and Allopurinol, followed by Melatonin, Clemastine, ß-Hydroxybutyrate, Omegaven, and Iodide. The probability of efficacy was superior to that of HT for Caffeine, SAG, Allopurinol, Melatonin, Clemastine, ß-hydroxybutyrate, and Omegaven. We provide the results of the first systematic preclinical screening of potential neuroprotective treatments and present alternative single therapies that may be promising treatment options for HT in LMIC. 000258240 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0 000258240 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000258240 650_7 $$2NLM Chemicals$$aNeuroprotective Agents 000258240 650_7 $$063CZ7GJN5I$$2NLM Chemicals$$aAllopurinol 000258240 650_7 $$0JL5DK93RCL$$2NLM Chemicals$$aMelatonin 000258240 650_7 $$03G6A5W338E$$2NLM Chemicals$$aCaffeine 000258240 650_7 $$095QN29S1ID$$2NLM Chemicals$$aClemastine 000258240 650_7 $$2NLM Chemicals$$aHedgehog Proteins 000258240 650_7 $$2NLM Chemicals$$aHydroxybutyrates 000258240 650_2 $$2MeSH$$aHumans 000258240 650_2 $$2MeSH$$aInfant, Newborn 000258240 650_2 $$2MeSH$$aAnimals 000258240 650_2 $$2MeSH$$aRats 000258240 650_2 $$2MeSH$$aNeuroprotective Agents: pharmacology 000258240 650_2 $$2MeSH$$aNeuroprotective Agents: therapeutic use 000258240 650_2 $$2MeSH$$aAnimals, Newborn 000258240 650_2 $$2MeSH$$aAllopurinol: pharmacology 000258240 650_2 $$2MeSH$$aMelatonin: pharmacology 000258240 650_2 $$2MeSH$$aMelatonin: therapeutic use 000258240 650_2 $$2MeSH$$aCaffeine: pharmacology 000258240 650_2 $$2MeSH$$aClemastine: pharmacology 000258240 650_2 $$2MeSH$$aHedgehog Proteins 000258240 650_2 $$2MeSH$$aBrain Injuries: drug therapy 000258240 650_2 $$2MeSH$$aBrain 000258240 650_2 $$2MeSH$$aHypothermia, Induced: methods 000258240 650_2 $$2MeSH$$aHypoxia-Ischemia, Brain: drug therapy 000258240 650_2 $$2MeSH$$aHypoxia: drug therapy 000258240 650_2 $$2MeSH$$aHydroxybutyrates: pharmacology 000258240 650_2 $$2MeSH$$aAsphyxia Neonatorum: drug therapy 000258240 650_2 $$2MeSH$$aDisease Models, Animal 000258240 650_2 $$2MeSH$$aIschemia: therapy 000258240 7001_ $$0P:(DE-2719)9001055$$aMaes, Elke$$b1$$udzne 000258240 7001_ $$0P:(DE-2719)9000835$$aZweyer, Margit$$b2$$udzne 000258240 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