0000000000381062
AUTHOR
Rønnaug Solberg
Metabolic adaptation and neuroprotection differ in the retina and choroid in a piglet model of acute postnatal hypoxia.
Hypoxic-ischemic insults to the neonatal brain may cause neurodevelopmental disorders. Vulnerability of different areas of the neural tissue to hypoxic-ischemic stress might be explained by either heterogeneous sensitivity to oxygen or neuroprotective capability. Our understanding of regional heterogeneity is still incomplete in terms of metabolic reconfiguration and/or activation of neuroprotective mechanisms.We studied, by western blotting, reverse-transcriptase PCR, and tandem mass spectrometry, the response of retina and choroid at protein, gene, and metabolic levels during hypoxia in a piglet model of acute postnatal hypoxia.We evidenced a metabolic shift towards glycolysis in choroid …
Detection of batch effects in liquid chromatography-mass spectrometry metabolomic data using guided principal component analysis.
Metabolomics based on liquid chromatography-mass spectrometry (LC-MS) is a powerful tool for studying dynamic responses of biological systems to different physiological or pathological conditions. Differences in the instrumental response within and between batches introduce unwanted and uncontrolled data variation that should be removed to extract useful information. This work exploits a recently developed method for the identification of batch effects in high throughput genomic data based on the calculation of a delta statistic through principal component analysis (PCA) and guided PCA. Its applicability to LC-MS metabolomic data was tested on two real examples. The first example involved t…
Protein-bound tyrosine oxidation, nitration and chlorination by-products assessed by ultraperformance liquid chromatography coupled to tandem mass spectrometry
Abstract Background Free radicals cause alterations in cellular protein structure and function. Oxidized, nitrated, and chlorinated modifications of aromatic amino acids including phenylalanine and tyrosine are reliable biomarkers of oxidative stress and inflammation in clinical conditions. Objective To develop, validate and apply a rapid method for the quantification of known hallmarks of tyrosine oxidation, nitration and chlorination in plasma and tissue proteins providing a snapshot of the oxidative stress and inflammatory status of the organism and of target organs respectively. Material and Methods The extraction and clean up procedure entailed protein precipitation, followed by protei…
N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia
<b><i>Background:</i></b> Perinatal asphyxia and ensuing reoxygenation change the antioxidant capacity of cells and organs. <b><i>Objectives:</i></b> To analyze the neuroprotective effect of the antioxidant N-acetylcysteine amide (NACA) after perinatal hypoxia-reoxygenation with an emphasis on proinflammatory cytokines and the transcription factor NF-&#x03BA;B in the prefrontal cortex of neonatal pigs. <b><i>Methods:</i></b> Twenty-nine newborn pigs, aged 12-36 h, were subjected to global hypoxia and hypercapnia. One sham-operated group (n = 5) and 2 experimental groups (n = 12) were exposed to 8% oxygen, until the …
34 Early Gene Regulation in Retina and Choroid After Ashpyxia and Resuscitation in Newborn Piglets
34 Early Gene Regulation in Retina and Choroid After Ashpyxia and Resuscitation in Newborn Piglets
Metabolomic Analysis of the Effect of Postnatal Hypoxia on the Retina in a Newly Born Piglet Model
The availability of reliable biomarkers of brain injury secondary to birth asphyxia could substantially improve clinical grading, therapeutic intervention strategies, and prognosis. In this study, changes in the metabolome of retinal tissue caused by profound hypoxia in an established neonatal piglet model were investigated using an ultra performance liquid chromatography - quadrupole time of flight mass spectrometry (UPLC-QTOFMS) untargeted metabolomic approach, which included Partial Least Squares - Discriminant Analysis (PLSDA) multivariate data analysis. The initial identification of a set of discriminant metabolites from UPLC-QTOFMS data was confirmed by target UPLC-MS/MS and allowed t…
Asphyxia Activates P65 and Induces VEGF-A Gene Expression in Retina and Choroid from Newborn Piglets
Objective: Exposure to lower oxygen causes oxidative stress and promotes angiogenesis. Asphyctic neonates have shown higher cord-blood vascular endothelial growth factor (VEGF). We hypothesized that retina and choroid having a different circulatory regulation (choroid lacks vascular auto-regulation) would acutely stimulate angiogenesis in response to short and severe hypoxemia.