Journal Article

DZNE-2024-00692

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Omega-3 fatty acid diglyceride emulsions as a novel injectable acute therapeutic in neonatal hypoxic-ischemic brain injury.

Zirpoli, H. ; Bernis, M. E.DZNE* ; Sabir, H.DZNE* ; Manual Kollareth, D. J. ; Hamilton, J. A. ; Huang, N. ; Ng, J. ; Sosunov, S. A. ; Gaebler, B. ; Ten, V. S. ; Deckelbaum, R. J.

2024
Elsevier Paris [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.biopha.2024.116749

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.

Keyword(s): Animals (MeSH) ; Hypoxia-Ischemia, Brain: drug therapy (MeSH) ; Animals, Newborn (MeSH) ; Fatty Acids, Omega-3: administration & dosage (MeSH) ; Fatty Acids, Omega-3: pharmacology (MeSH) ; Emulsions (MeSH) ; Mice (MeSH) ; Neuroprotective Agents: administration & dosage (MeSH) ; Neuroprotective Agents: pharmacology (MeSH) ; Rats (MeSH) ; Rats, Sprague-Dawley (MeSH) ; Mice, Inbred C57BL (MeSH) ; Disease Models, Animal (MeSH) ; Male (MeSH) ; Brain: drug effects (MeSH) ; Brain: metabolism (MeSH) ; Brain: pathology (MeSH) ; diglycerides ; gliosis ; hypoxic-ischemic encephalopathy ; lipid emulsion ; neuroprotection ; omega-3 fatty acids ; Fatty Acids, Omega-3 ; Emulsions ; Neuroprotective Agents

Note: ISSN 0753-3322 not unique: **2 hits**.

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Contributing Institute(s):

1. Neonatal Neuroscience (AG Sabir)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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