TY  - JOUR
AU  - Zirpoli, Hylde
AU  - Bernis, Maria Eugenia
AU  - Sabir, Hemmen
AU  - Manual Kollareth, Denny Joseph
AU  - Hamilton, James A
AU  - Huang, Nasi
AU  - Ng, Jesse
AU  - Sosunov, Sergey A
AU  - Gaebler, Ben
AU  - Ten, Vadim S
AU  - Deckelbaum, Richard J
TI  - Omega-3 fatty acid diglyceride emulsions as a novel injectable acute therapeutic in neonatal hypoxic-ischemic brain injury.
JO  - Biomedicine & pharmacotherapy
VL  - 175
SN  - 0300-0893
CY  - Paris [u.a.]
PB  - Elsevier
M1  - DZNE-2024-00692
SP  - 116749
PY  - 2024
N1  - ISSN 0753-3322 not unique: **2 hits**.
AB  - 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.
KW  - Animals
KW  - Hypoxia-Ischemia, Brain: drug therapy
KW  - Animals, Newborn
KW  - Fatty Acids, Omega-3: administration & dosage
KW  - Fatty Acids, Omega-3: pharmacology
KW  - Emulsions
KW  - Mice
KW  - Neuroprotective Agents: administration & dosage
KW  - Neuroprotective Agents: pharmacology
KW  - Rats
KW  - Rats, Sprague-Dawley
KW  - Mice, Inbred C57BL
KW  - Disease Models, Animal
KW  - Male
KW  - Brain: drug effects
KW  - Brain: metabolism
KW  - Brain: pathology
KW  - diglycerides (Other)
KW  - gliosis (Other)
KW  - hypoxic-ischemic encephalopathy (Other)
KW  - lipid emulsion (Other)
KW  - neuroprotection (Other)
KW  - omega-3 fatty acids (Other)
KW  - Fatty Acids, Omega-3 (NLM Chemicals)
KW  - Emulsions (NLM Chemicals)
KW  - Neuroprotective Agents (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11156760
C6  - pmid:38761420
DO  - DOI:10.1016/j.biopha.2024.116749
UR  - https://pub.dzne.de/record/269866
ER  -