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@ARTICLE{Sabir:258240,
      author       = {Sabir, Hemmen and Maes, Elke and Zweyer, Margit and
                      Schleehuber, Yvonne and Imam, Farhad B and Silverman, Jared
                      and White, Yasmine and Pang, Raymand and Pasca, Anca M and
                      Robertson, Nicola J and Maltepe, Emin and Bernis, Maria
                      Eugenia},
      title        = {{C}omparing the efficacy in reducing brain injury of
                      different neuroprotective agents following neonatal
                      hypoxia-ischemia in newborn rats: a multi-drug randomized
                      controlled screening trial.},
      journal      = {Scientific reports},
      volume       = {13},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DZNE-2023-00586},
      pages        = {9467},
      year         = {2023},
      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.},
      keywords     = {Humans / Infant, Newborn / Animals / Rats / Neuroprotective
                      Agents: pharmacology / Neuroprotective Agents: therapeutic
                      use / Animals, Newborn / Allopurinol: pharmacology /
                      Melatonin: pharmacology / Melatonin: therapeutic use /
                      Caffeine: pharmacology / Clemastine: pharmacology / Hedgehog
                      Proteins / Brain Injuries: drug therapy / Brain /
                      Hypothermia, Induced: methods / Hypoxia-Ischemia, Brain:
                      drug therapy / Hypoxia: drug therapy / Hydroxybutyrates:
                      pharmacology / Asphyxia Neonatorum: drug therapy / Disease
                      Models, Animal / Ischemia: therapy / Neuroprotective Agents
                      (NLM Chemicals) / Allopurinol (NLM Chemicals) / Melatonin
                      (NLM Chemicals) / Caffeine (NLM Chemicals) / Clemastine (NLM
                      Chemicals) / Hedgehog Proteins (NLM Chemicals) /
                      Hydroxybutyrates (NLM Chemicals)},
      cin          = {AG Sabir},
      ddc          = {600},
      cid          = {I:(DE-2719)5000032},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37301929},
      pmc          = {pmc:PMC10257179},
      doi          = {10.1038/s41598-023-36653-9},
      url          = {https://pub.dzne.de/record/258240},
}