Oxygen dependency of mitochondrial metabolism indicates outcome of newborn brain injury

Gemma Bale, Subhabrata Mitra, Isabel de Roever, Magdalena Sokolska, David Price, Alan Bainbridge, Roxana Gunny, Cristina Uria-Avellanal, Giles S Kendall, Judith Meek, Nicola J Robertson, Ilias Tachtsidis

Research output: Contribution to journalArticlepeer-review

Abstract

There is a need for a method of real-time assessment of brain metabolism during neonatal hypoxic-ischaemic encephalopathy (HIE). We have used broadband near-infrared spectroscopy (NIRS) to monitor cerebral oxygenation and metabolic changes in 50 neonates with HIE undergoing therapeutic hypothermia treatment. In 24 neonates, 54 episodes of spontaneous decreases in peripheral oxygen saturation (desaturations) were recorded between 6 and 81 h after birth. We observed differences in the cerebral metabolic responses to these episodes that were related to the predicted outcome of the injury, as determined by subsequent magnetic resonance spectroscopy derived lactate/N-acetyl-aspartate. We demonstrated that a strong relationship between cerebral metabolism (broadband NIRS-measured cytochrome-c-oxidase (CCO)) and cerebral oxygenation was associated with unfavourable outcome; this is likely to be due to a lower cerebral metabolic rate and mitochondrial dysfunction in severe encephalopathy. Specifically, a decrease in the brain tissue oxidation state of CCO greater than 0.06 µM per 1 µM brain haemoglobin oxygenation drop was able to predict the outcome with 64% sensitivity and 79% specificity (receiver operating characteristic area under the curve = 0.73). With further work on the implementation of this methodology, broadband NIRS has the potential to provide an early, cotside, non-invasive, clinically relevant metabolic marker of perinatal hypoxic-ischaemic injury.

Original languageEnglish
Pages (from-to)2035-2047
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume39
Issue number10
DOIs
Publication statusPublished - Oct 2019

Keywords

  • Brain/blood supply
  • Brain Injuries/complications
  • Cerebrovascular Circulation
  • Female
  • Humans
  • Hypothermia, Induced/methods
  • Hypoxia/complications
  • Infant, Newborn
  • Male
  • Mitochondria/metabolism
  • Oxygen/metabolism
  • Prospective Studies
  • Treatment Outcome

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