Brain mitochondrial oxidative metabolism during and after cerebral hypoxia-ischemia studied by simultaneous phosphorus magnetic-resonance and broadband near-infrared spectroscopy

A Bainbridge, I Tachtsidis, S D Faulkner, D Price, T Zhu, E Baer, K D Broad, D L Thomas, E B Cady, N J Robertson, X Golay

Research output: Contribution to journalReview articlepeer-review

Abstract

BACKGROUND: Multimodal measurements combining broadband near-infrared spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy ((31)P MRS) assessed associations between changes in the oxidation state of cerebral mitochondrial cytochrome-c-oxidase (Δ[oxCCO]) and (31)P metabolite peak-area ratios during and after transient cerebral hypoxia-ischemia (HI) in the newborn piglet.

METHODS: Twenty-four piglets (aged<24 h) underwent transient HI (inspired oxygen fraction 9% and bilateral carotid artery occlusion for ~20 min). Whole-brain (31)P MRS and NIRS data were acquired every minute. Inorganic phosphate (Pi)/epp, phosphocreatine (PCr)/epp, and total nucleotide triphosphate (NTP)/epp were measured by (31)P MRS and were plotted against Δ[oxCCO] during HI and recovery (epp=exchangeable phosphate pool=Pi+PCr+2γ-NTP+β-NTP).

RESULTS: During HI Δ[oxCCO], PCr/epp and NTP/epp declined and Pi/epp increased. Significant correlations were seen between (31)P ratios and Δ[oxCCO]; during HI a threshold point was identified where the relationship between Δ[oxCCO] and both NTP/epp and Pi/epp changed significantly. Outcome at 48 h related to recovery of Δ[oxCCO] and (31)P ratios 1h post-HI (survived: 1-h NTP/epp 0.22 ± 0.02, Δ[oxCCO] -0.29 ± 0.50 μM; died: 1-h NTP/epp 0.10 ± 0.04, Δ[oxCCO] -2.41 ± 1.48 μM).

CONCLUSIONS: Both lowered Δ[oxCCO] and NTP/epp 1h post-HI indicated mitochondrial impairment. Animals dying before 48 h had slower recovery of both Δ[oxCCO] and (31)P ratios by 1 h after HI.

Original languageEnglish
Pages (from-to)173-83
Number of pages11
JournalNeuroImage
Volume102 Pt 1
DOIs
Publication statusPublished - 15 Nov 2014

Keywords

  • Animals
  • Hypoxia-Ischemia, Brain/metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Mitochondria/metabolism
  • Oxidation-Reduction
  • Phosphorus Isotopes
  • Spectroscopy, Near-Infrared
  • Swine

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