Elsevier

NeuroImage

Volume 102, Part 1, 15 November 2014, Pages 173-183
NeuroImage

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

https://doi.org/10.1016/j.neuroimage.2013.08.016Get rights and content
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Highlights

  • 31P MRS correlated with broadband NIRS during and after transient hypoxia–ischemia.

  • A double-linear model best describes NTP/epp vs Δ[oxCCO] during HI.

  • Threshold point in double-linear model interpreted as cessation of ATP manufacture.

  • Poor outcome correlates with weaker recovery of both 31P MRS ratios and Δ[oxCCO].

  • Mitochondrial dysfunction may be the cause of reduction of Δ[oxCCO].

Abstract

Background

Multimodal measurements combining broadband near-infrared spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy (31P MRS) assessed associations between changes in the oxidation state of cerebral mitochondrial cytochrome-c-oxidase (Δ[oxCCO]) and 31P 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 31P MRS and NIRS data were acquired every minute. Inorganic phosphate (Pi)/epp, phosphocreatine (PCr)/epp, and total nucleotide triphosphate (NTP)/epp were measured by 31P 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 31P 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 31P ratios 1 h 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 1 h post-HI indicated mitochondrial impairment. Animals dying before 48 h had slower recovery of both Δ[oxCCO] and 31P ratios by 1 h after HI.

Keywords

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

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