% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@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},
}