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@ARTICLE{Zirpoli:269866,
author = {Zirpoli, Hylde and Bernis, Maria Eugenia and Sabir, Hemmen
and Manual Kollareth, Denny Joseph and Hamilton, James A and
Huang, Nasi and Ng, Jesse and Sosunov, Sergey A and Gaebler,
Ben and Ten, Vadim S and Deckelbaum, Richard J},
title = {{O}mega-3 fatty acid diglyceride emulsions as a novel
injectable acute therapeutic in neonatal hypoxic-ischemic
brain injury.},
journal = {Biomedicine $\&$ pharmacotherapy},
volume = {175},
issn = {0300-0893},
address = {Paris [u.a.]},
publisher = {Elsevier},
reportid = {DZNE-2024-00692},
pages = {116749},
year = {2024},
note = {ISSN 0753-3322 not unique: **2 hits**.},
abstract = {Hypoxic-ischemic encephalopathy (HIE), resulting from a
lack of blood flow and oxygen before or during newborn
delivery, is a leading cause of cerebral palsy and
neurological disability in children. Therapeutic hypothermia
(TH), the current standard of care in HIE, is only
beneficial in 1 of 7-8 cases. Therefore, there is a critical
need for more efficient treatments. We have previously
reported that omega-3 (n-3) fatty acids (FA) carried by
triglyceride (TG) lipid emulsions provide neuroprotection
after experimental hypoxic-ischemic (HI) injury in neonatal
mice. Herein, we propose a novel acute therapeutic approach
using an n-3 diglyceride (DG) lipid emulsions. Importantly,
n-3 DG preparations had much smaller particle size compared
to commercially available or lab-made n-3 TG emulsions. We
showed that n-3 DG molecules have the advantage of
incorporating at substantially higher levels than n-3 TG
into an in vitro model of phospholipid membranes. We also
observed that n-3 DG after parenteral administration in
neonatal mice reaches the bloodstream more rapidly than n-3
TG. Using neonatal HI brain injury models in mice and rats,
we found that n-3 DG emulsions provide superior
neuroprotection than n-3 TG emulsions or TH in decreasing
brain infarct size. Additionally, we found that n-3 DGs
attenuate microgliosis and astrogliosis. Thus, n-3 DG
emulsions are a superior, promising, and novel therapy for
treating HIE.},
keywords = {Animals / Hypoxia-Ischemia, Brain: drug therapy / Animals,
Newborn / Fatty Acids, Omega-3: administration $\&$ dosage /
Fatty Acids, Omega-3: pharmacology / Emulsions / Mice /
Neuroprotective Agents: administration $\&$ dosage /
Neuroprotective Agents: pharmacology / Rats / Rats,
Sprague-Dawley / Mice, Inbred C57BL / Disease Models, Animal
/ Male / Brain: drug effects / Brain: metabolism / Brain:
pathology / diglycerides (Other) / gliosis (Other) /
hypoxic-ischemic encephalopathy (Other) / lipid emulsion
(Other) / neuroprotection (Other) / omega-3 fatty acids
(Other) / Fatty Acids, Omega-3 (NLM Chemicals) / Emulsions
(NLM Chemicals) / Neuroprotective Agents (NLM Chemicals)},
cin = {AG Sabir},
ddc = {610},
cid = {I:(DE-2719)5000032},
pnm = {352 - Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC11156760},
pubmed = {pmid:38761420},
doi = {10.1016/j.biopha.2024.116749},
url = {https://pub.dzne.de/record/269866},
}