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Neuroimage. 2014 Nov 15;102 Pt 1:173-83. doi: 10.1016/j.neuroimage.2013.08.016. Epub 2013 Aug 17.

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

Author information

1
Medical Physics and Bioengineering, UCLH NHS Foundation Trust, London NW1 2BU, UK. Electronic address: alan.bainbridge@uclh.nhs.uk.
2
Medical Physics and Bioengineering, University College London, WC1E 6BT, UK.
3
Institute for Women's Health, University College London, WC1E 6AU, UK.
4
Medical Physics and Bioengineering, UCLH NHS Foundation Trust, London NW1 2BU, UK.
5
Institute of Neurology, University College London, London WC1N 3BG, UK.

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.

KEYWORDS:

(31)P; Cytochrome-c-oxidase; Hypoxia–ischemia; MRS; NIRS; Phosphorus

PMID:
23959202
PMCID:
PMC4229502
DOI:
10.1016/j.neuroimage.2013.08.016
[Indexed for MEDLINE]
Free PMC Article

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