ArticleScientific reports2023
Comparing the efficacy in reducing brain injury of different neuroprotective agents following neonatal hypoxia-ischemia in newborn rats: a multi-drug randomized controlled screening trial.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 33 citations in OpenAlex.
- Trial of Edaravone for severe hypoxic ischemic encephalopathy in adults: a double-blind placebo-controlled study.Journal of neurology · 2026Trial
- NLRP3 Regulation in Neonatal Hypoxic-Ischemic Encephalopathy-Focus on Microglial Activation.International journal of molecular sciences · 2026Article
- Article
- Therapeutic hypothermia in infants <36 weeks gestation: proceed with caution.Pediatric research · 2026Article
- Comparing neuroprotective drug efficacy in rodent neonatal brain injury models.Pediatric research · 2026Article
- Cumulative caffeine exposure predicts neurodevelopmental outcomes in premature infants.Pediatric research · 2026Article
- Benefits and risks of therapeutic hypothermia for hypoxic-ischemic encephalopathy in late preterm infants.Pediatric research · 2026Review
- Drug development for newborn brain injury.Pediatric research · 2026Article
- Multi-modal screening for synergistic neuroprotection of mild extremely preterm brain injury.Bioengineering & translational medicine · 2026Article
- Use of Laser Speckle Contrast Imaging for Distribution of Animals by Severity of Brain Tissue Damage in a Neonatal Hypoxia-Ischemia Model in Mice.Brain sciences · 2026Article
- Advancements in Neonatal Brain Injury Treatment: Nanomedicine-Based Strategies.International journal of nanomedicine · 2026Review
- Caffeine as a Treatment for Perinatal Hypoxic-Ischemic Brain Injury: The Potential Risks and Benefits.Developmental neuroscience · 2026Review
- Comparing Neuroprotective Drug Efficacy in Rodent Neonatal Brain Injury Models.bioRxiv : the preprint server for biology · 2025Article
- Population Pharmacokinetics of Caffeine in Infants with Hypoxic-Ischemic Encephalopathy: A Phase I, Dose-Escalating Trial.Journal of clinical pharmacology · 2025Article
- Neuroprotection for neonatal hypoxic-ischemic encephalopathy: A review of novel therapies evaluated in clinical studies.Developmental medicine and child neurology · 2025Review
- The Neuroprotective Effects of Caffeine in a Neonatal Hypoxia-Ischemia Model are Regulated through the AMPK/mTOR Pathway.International journal of biological sciences · 2025Article
- Antioxidant Therapy in Neonatal Hypoxic Ischemic Encephalopathy: Adjuvant or Future Alternative to Therapeutic Hypothermia?Metabolites · 2024Review
- Perinatal Caffeine Administration Improves Outcomes in an Ovine Model of Neonatal Hypoxia-Ischemia.Stroke · 2024Article
- Neuroprotective Effect of Melatonin in a Neonatal Hypoxia-Ischemia Rat Model Is Regulated by the AMPK/mTOR Pathway.Journal of the American Heart Association · 2024Article
- Methylxanthine use in infants with hypoxic-ischemic encephalopathy: a retrospective cohort study.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intrapartum 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.
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