%0 Journal Article
%A Zirpoli, Hylde
%A Bernis, Maria Eugenia
%A Sabir, Hemmen
%A Manual Kollareth, Denny Joseph
%A Hamilton, James A
%A Huang, Nasi
%A Ng, Jesse
%A Sosunov, Sergey A
%A Gaebler, Ben
%A Ten, Vadim S
%A Deckelbaum, Richard J
%T Omega-3 fatty acid diglyceride emulsions as a novel injectable acute therapeutic in neonatal hypoxic-ischemic brain injury.
%J Biomedicine & pharmacotherapy
%V 175
%@ 0300-0893
%C Paris [u.a.]
%I Elsevier
%M DZNE-2024-00692
%P 116749
%D 2024
%Z ISSN 0753-3322 not unique: **2 hits**.
%X 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.
%K Animals
%K Hypoxia-Ischemia, Brain: drug therapy
%K Animals, Newborn
%K Fatty Acids, Omega-3: administration & dosage
%K Fatty Acids, Omega-3: pharmacology
%K Emulsions
%K Mice
%K Neuroprotective Agents: administration & dosage
%K Neuroprotective Agents: pharmacology
%K Rats
%K Rats, Sprague-Dawley
%K Mice, Inbred C57BL
%K Disease Models, Animal
%K Male
%K Brain: drug effects
%K Brain: metabolism
%K Brain: pathology
%K diglycerides (Other)
%K gliosis (Other)
%K hypoxic-ischemic encephalopathy (Other)
%K lipid emulsion (Other)
%K neuroprotection (Other)
%K omega-3 fatty acids (Other)
%K Fatty Acids, Omega-3 (NLM Chemicals)
%K Emulsions (NLM Chemicals)
%K Neuroprotective Agents (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%2 pmc:PMC11156760
%$ pmid:38761420
%R 10.1016/j.biopha.2024.116749
%U https://pub.dzne.de/record/269866