title: 1H nuclear magnetic resonance brain metabolomics in neonatal mice after hypoxia-ischemia distinguished normothermic recovery from mild hypothermia recoveries.
abstract: BACKGROUND
  Mild brain hypothermia (31-34 °C) after neonatal hypoxia-ischemia (HI) improves neurodevelopmental outcomes in human and animal neonates. Using an asphyxia model with neonatal mice treated with mild hypothermia after HI, we investigated whether (1)H nuclear magnetic resonance (NMR) metabolomics of brain extracts could suggest biomarkers and distinguish different treatments and outcome groups.
  
  
  METHODS
  At postnatal day 7 (P7), CD1 mice underwent right carotid artery occlusion, 30 min of HI (8% oxygen), and 3.5 h of either hypothermia (31 °C) or normothermia (37 °C). Whole brains were frozen immediately after HI, immediately after 3.5 h of hypothermia or normothermia treatments, and 24 h later. Perchloric acid extractions of 36 metabolites were quantified by 900 MHz (1)H NMR spectroscopy. Multivariate analyses included principal component analyses (PCA) and a novel regression algorithm. Histological injury was quantified after HI at 5 d.
  
  
  RESULTS
  PCA scores plots separated normothermia/HI animals from hypothermia/HI and control animals, but more data are required for multivariate models to be predictive. Loadings plots identified 11 significant metabolites, whereas the regression algorithm identified 6. Histological injury scores were significantly reduced by hypothermia.
  
  
  CONCLUSIONS
  Different treatment and outcome groups are identifiable by (1)H NMR metabolomics in a neonatal mouse model of mild hypothermia treatment of HI.
authors.affiliation: Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: R Ann
authors.initials: RA
authors.lastname: Sheldon
authors.forename: Mark R
authors.initials: MR
authors.lastname: Segal
authors.forename: Mark J S
authors.initials: MJ
authors.lastname: Kelly
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Pelton
authors.forename: Donna M
authors.initials: DM
authors.lastname: Ferriero
authors.forename: Thomas L
authors.initials: TL
authors.lastname: James
authors.forename: Lawrence
authors.initials: L
authors.lastname: Litt
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D007036:Hypothermia, Induced / Q000379:methods*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000628:therapy*; D009682:Magnetic Resonance Spectroscopy; D055442:Metabolome / Q000235:genetics / Q000502:physiology*; D055432:Metabolomics; D051379:Mice; D025341:Principal Component Analysis; D012044:Regression Analysis