title: Metabolic adaptation and neuroprotection differ in the retina and choroid in a piglet model of acute postnatal hypoxia.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  We evidenced a metabolic shift towards glycolysis in choroid after hypoxia while retina experienced a dramatic energy stress with decreased mitochondrial metabolites. Hypoxia-inducible transcription factor-1α (HIF-1α) was not stabilized in retina during hypoxia, supported by a deficient signaling from v-akt murine thymoma viral oncogene (AKT) and ERK1/2, and unchanged glutathione redox status. In retina, but not in choroid, phosphorylation of p65 (NF-κB) and increased transcription of target genes may have a major role during hypoxic stress.
  
  
  CONCLUSIONS
  We showed that the retina engages a distinct pattern of signaling and transcriptional events than observed in the choroid. Retina and choroid may reflect regional sensitivity to hypoxia. While prolonged and intense hypoxia may jeopardize retinal cell survival, choroid sets up a different pattern of response, which promotes adaptation to these adverse conditions.
authors.affiliation: 1] Department of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain [2] Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Arduini
authors.affiliation: Neonatal Research Unit, Health Research Institute La Fe, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Escobar
authors.affiliation: 1] Neonatal Research Unit, Health Research Institute La Fe, Valencia, Spain [2] Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain.
authors.forename: Maximo
authors.initials: M
authors.lastname: Vento
authors.affiliation: Division of Neonatology, University and Polytechnic Hospital La Fe, Valencia, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Escrig
authors.affiliation: Leitat Technological Center, Bio In Vitro Division, Barcelona, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Quintás
authors.affiliation: Department of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Sastre
authors.affiliation: Department of Pediatric Research, Institute for Surgical Research, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
authors.forename: Ola Didrik
authors.initials: OD
authors.lastname: Saugstad
authors.affiliation: Department of Pediatric Research, Institute for Surgical Research, Oslo University Hospital-Rikshospitalet, Oslo, Norway.
authors.forename: Rønnaug
authors.initials: R
authors.lastname: Solberg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002829:Choroid / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D006019:Glycolysis / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*; D013552:Swine; D053719:Tandem Mass Spectrometry
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit