Details

Autor(en) / Beteiligte

• Manual Kollareth, Denny Joseph
• Deckelbaum, Richard J.
• Liu, Zequn
• Ramakrishnan, Rajasekhar
• Jouvene, Charlotte
• Serhan, Charles N.
• Ten, Vadim S.
• Zirpoli, Hylde

Titel

Acute injection of a DHA triglyceride emulsion after hypoxic-ischemic brain injury in mice increases both DHA and EPA levels in blood and brain

Ist Teil von

• Prostaglandins, leukotrienes and essential fatty acids, 2020-11, Vol.162, p.102176-102176, Article 102176

Ort / Verlag

Scotland: Elsevier Ltd

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• •DHA injected as triglyceride emulsion (tri-DHA) was associated with highest uptake in the liver while brain has the lowest.•Rapid increases in plasma LPC-DHA levels were observed in animals subjected to ischemic injury and acutely treated with tri-DHA.•Tri-DHA administration increased DHA derived SPMs in brain after ischemic injury.•Tri-DHA administration increased EPA and EPA derived SPMs and pathway markers in plasma lipid pools and in brain. We recently reported that acute injection of docosahexaenoic acid (DHA) triglyceride emulsions (tri-DHA) conferred neuroprotection after hypoxic-ischemic (HI) injury in a neonatal mouse stroke model. We showed that exogenous DHA increased concentrations of DHA in brain mitochondria as well as DHA-derived specialized pro-resolving mediator (SPM) levels in the brain. The objective of the present study was to investigate the distribution of emulsion particles and changes in plasma lipid profiles after tri-DHA injection in naïve mice and in animals subjected to HI injury. We also examined whether tri-DHA injection would change DHA- and eicosapentaenoic acid (EPA)-derived SPM levels in the brain. To address this, neonatal (10-day-old) naïve and HI mice were injected with radiolabeled tri-DHA emulsion (0.375 g tri-DHA/kg bw), and blood clearance and tissue distribution were analyzed. Among all the organs assayed, the lowest uptake of emulsion particles was in the brain (<0.4% recovered dose) in both naïve and HI mice, while the liver had the highest uptake. Tri-DHA administration increased DHA concentrations in plasma lysophosphatidylcholine and non-esterified fatty acids. Additionally, treatment with tri-DHA after HI injury significantly elevated the levels of DHA-derived SPMs and monohydroxy-containing DHA-derived products in the brain. Further, tri-DHA administration increased resolvin E2 (RvE2, 5S,18R-dihydroxy-eicosa-6E,8Z,11Z,14Z,16E-pentaenoic acid) and monohydroxy-containing EPA-derived products in the brain. These results suggest that the transfer of DHA through plasma lipid pools plays an important role in DHA brain transport in neonatal mice subjected to HI injury. Furthermore, increases in EPA and EPA-derived SPMs following tri-DHA injection demonstrate interlinked metabolism of these two fatty acids. Hence, changes in both EPA and DHA profile patterns need to be considered when studying the protective effects of DHA after HI brain injury. Our results highlight the need for further investigation to differentiate the effects of DHA from EPA on neuroprotective pathways following HI damage. Such information could contribute to the development of specific DHA-EPA formulations to improve clinical endpoints and modulate potential biomarkers in ischemic brain injury. [Display omitted]