Regional differences of hypothermia on oxidative stress following hypoxia-ischemia: a study of DHA and hypothermia on brain lipid peroxidation in newborn piglets.
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.
['Huun|Marianne U|MU|', 'Garberg|Håvard T|HT|', 'Buonocore|Giuseppe|G|', 'Longini|Mariangela|M|', 'Belvisi|Elisa|E|', 'Bazzini|Francesco|F|', 'Proietti|Fabrizio|F|', 'Saugstad|Ola Didrik|OD|', 'Solberg|Rønnaug|R|']
D000818:Animals D000831:Animals, Newborn D002853:Chromatography, Liquid D005231:Fatty Acids, Unsaturated D005260:Female D006624:Hippocampus D006801:Humans D007036:Hypothermia, Induced D020925:Hypoxia-Ischemia, Brain D028421:Isoprostanes D015227:Lipid Peroxidation D013058:Mass Spectrometry D018384:Oxidative Stress D017397:Prefrontal Cortex D011247:Pregnancy D013552:Swine D016896:Treatment Outcome D066127:White Matter
oxidative stress DHA lipid peroxidation therapeutic hypothermia isoprostanes neuroprostanes white matter injury