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Regional differences of hypothermia on oxidative stress following hypoxia-ischemia: a study of DHA and hypothermia on brain lipid peroxidation in newborn piglets

  • Marianne U. Huun EMAIL logo , Håvard T. Garberg , Giuseppe Buonocore , Mariangela Longini , Elisa Belvisi , Francesco Bazzini , Fabrizio Proietti , Ola Didrik Saugstad and Rønnaug Solberg
Published/Copyright: August 15, 2018
Journal of Perinatal Medicine
From the journal Journal of Perinatal Medicine Volume 47 Issue 1

Abstract

Background

Oxidative stress plays an important part in the pathophysiology of hypoxic-ischemic encephalopathy (HIE) and is reliably measured through prostanoids following lipid peroxidation of polyunsaturated fatty acids (PUFAs). The aim of the study is to measure oxidative stress in the prefrontal cortex, white matter and hippocampus in the brains of hypoxic-ischemic piglets treated with docosahexaenoic acid (DHA) and therapeutic hypothermia (TH) and investigate the additive effects of DHA on hypothermia by factorial design.

Methods

Fifty-five piglets were randomized as having severe global hypoxia (n=48) or not (sham, n=7). Hypoxic piglets were further randomized: vehicle (VEH), DHA, VEH+hypothermia (HT) or HT+DHA. A total of 5 mg/kg DHA was given intravenously 210 min after the end of hypoxia. Brain tissues were analyzed using liquid chromatography triple quadrupole mass spectrometry technique (LC-MS). A two-way analysis of variance (ANOVA) was performed with DHA and HT as main effects.

Results

In the white matter, we found main effects of DHA on DH-isoprostanes (P=0.030) and a main effect of HT on F4-neuroprostanes (F4-NeuroPs) (P=0.007), F2-isoprostanes (F2-IsoPs) (P=0.043) and DH-isoprostanes (P=0.023).

In the cortex, the ANOVA analysis showed the interactions of main effects between DHA and HT for neurofuranes (NeuroFs) (P=0.092) and DH-isoprostanes (P=0.015) as DHA significantly reduced lipid peroxidation in the absence of HT. DHA compared to VEH significantly reduced NeuroFs (P=0.019) and DH-isoprostanes (P=0.010). No differences were found in the hippocampus.

Conclusion

After severe hypoxia, HT reduced lipid peroxidation in the white matter but not in the cortical gray matter. HT attenuated the reducing effect of DHA on lipid peroxidation in the cortex. Further studies are needed to determine whether DHA can be an effective add-on therapy for TH.

Keywords: DHA; isoprostanes; lipid peroxidation; neuroprostanes; oxidative stress; therapeutic hypothermia; white matter injury

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpm-2017-0355).

Received: 2017-08-14
Accepted: 2018-04-11
Published Online: 2018-08-15
Published in Print: 2018-12-19

©2019 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/jpm-2017-0355
Keywords for this article
DHA; isoprostanes; lipid peroxidation; neuroprostanes; oxidative stress; therapeutic hypothermia; white matter injury

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Ductus venosus agenesis and fetal malformations: what can we expect? – a systematic review of the literature
  4. Opinion Paper
  5. Abnormally invasive placenta (AIP): pre-cesarean amnion drainage to facilitate exteriorization of the gravid uterus through a transverse skin incision
  6. Corner of Academy
  7. Midwife-assisted planned home birth: an essential component of improving the safety of childbirth in Sub-Saharan Africa
  8. Research Articles – Obstetrics
  9. Maternal body height is a stronger predictor of birth weight than ethnicity: analysis of birth weight percentile charts
  10. Chromosomal microarray findings in pregnancies with an isolated pelvic kidney
  11. Serum sFlt-1/PlGF ratio has better diagnostic ability in early- compared to late-onset pre-eclampsia
  12. A multidisciplinary approach to pregnancy loss: the pregnancy loss prevention center
  13. Relationship between intercellular adhesion molecule-1 and morbidly adherent placenta
  14. Birth risks according to maternal height and weight – an analysis of the German Perinatal Survey
  15. Research Articles – Fetus
  16. Untimely diagnosis of fetomaternal hemorrhage: what went wrong?
  17. Quantification of fetal myocardial function in pregnant women with diabetic diseases and in normal controls using speckle tracking echocardiography (STE)
  18. Prediction of postnatal developmental disabilities using the antenatal fetal neurodevelopmental test: KANET assessment
  19. Research Articles – Newborn
  20. Regional differences of hypothermia on oxidative stress following hypoxia-ischemia: a study of DHA and hypothermia on brain lipid peroxidation in newborn piglets
  21. Detection of cytomegalovirus in saliva from infants undergoing sepsis evaluation in the neonatal intensive care unit: the VIRIoN-C study
  22. Adverse neonatal outcomes and house prices in London
  23. A prospective analysis of intake and composition of mother’s own milk in preterm newborns less than 32 weeks’ gestational age
  24. Neonatal Ogg1/Mutyh knockout mice have altered inflammatory gene response compared to wildtype mice in the brain and lung after hypoxia-reoxygenation
  25. From single-case analysis of neonatal deaths toward a further reduction of the neonatal mortality rate
  26. Short Communication
  27. Comparison of two different treatments in depressed pregnant women: fetal growth characteristics and neonatal outcomes
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