Home > Publications Database > 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. > print

001     258240
005     20231004134645.0
024 7 _ |a 10.1038/s41598-023-36653-9
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100 1 _ |a Sabir, Hemmen
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245 _ _ |a 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.
260 _ _ |a [London]
|c 2023
|b Macmillan Publishers Limited, part of Springer Nature
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520 _ _ |a 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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650 _ 7 |a Neuroprotective Agents
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650 _ 7 |a Allopurinol
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650 _ 7 |a Melatonin
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650 _ 7 |a Caffeine
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650 _ 7 |a Clemastine
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650 _ 7 |a Hedgehog Proteins
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650 _ 7 |a Hydroxybutyrates
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650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Infant, Newborn
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Rats
|2 MeSH
650 _ 2 |a Neuroprotective Agents: pharmacology
|2 MeSH
650 _ 2 |a Neuroprotective Agents: therapeutic use
|2 MeSH
650 _ 2 |a Animals, Newborn
|2 MeSH
650 _ 2 |a Allopurinol: pharmacology
|2 MeSH
650 _ 2 |a Melatonin: pharmacology
|2 MeSH
650 _ 2 |a Melatonin: therapeutic use
|2 MeSH
650 _ 2 |a Caffeine: pharmacology
|2 MeSH
650 _ 2 |a Clemastine: pharmacology
|2 MeSH
650 _ 2 |a Hedgehog Proteins
|2 MeSH
650 _ 2 |a Brain Injuries: drug therapy
|2 MeSH
650 _ 2 |a Brain
|2 MeSH
650 _ 2 |a Hypothermia, Induced: methods
|2 MeSH
650 _ 2 |a Hypoxia-Ischemia, Brain: drug therapy
|2 MeSH
650 _ 2 |a Hypoxia: drug therapy
|2 MeSH
650 _ 2 |a Hydroxybutyrates: pharmacology
|2 MeSH
650 _ 2 |a Asphyxia Neonatorum: drug therapy
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Ischemia: therapy
|2 MeSH
700 1 _ |a Maes, Elke
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700 1 _ |a Zweyer, Margit
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700 1 _ |a Schleehuber, Yvonne
|0 P:(DE-2719)2811751
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700 1 _ |a Imam, Farhad B
|b 4
700 1 _ |a Silverman, Jared
|b 5
700 1 _ |a White, Yasmine
|b 6
700 1 _ |a Pang, Raymand
|b 7
700 1 _ |a Pasca, Anca M
|b 8
700 1 _ |a Robertson, Nicola J
|b 9
700 1 _ |a Maltepe, Emin
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700 1 _ |a Bernis, Maria Eugenia
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773 _ _ |a 10.1038/s41598-023-36653-9
|g Vol. 13, no. 1, p. 9467
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|t Scientific reports
|v 13
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