The relationship between cytochrome c oxidase, CBF and CMRO2 in mouse cortex: A NIRS-MRI study

J Cereb Blood Flow Metab. 2023 Aug;43(8):1351-1364. doi: 10.1177/0271678X231165842. Epub 2023 Mar 23.

Abstract

Quantifying relationships between cerebral blood flow (CBF), mitochondrial function (cytochrome c oxidase oxidation state), and metabolic rate of oxygen (CMRO2) could provide useful insight into normal neurovascular coupling, as well as regulation of oxidative metabolism in neurological disorders. This paper uses a multimodal NIRS-MRI method to quantify these parameters in rodent brain and, in so doing, provides novel information on the regulation of oxygen metabolism by stimulating with hypercapnia or variations in oxygenation. Under hypercapnia, although oxygenation, oxidation state, and CBF increased, there was no increase in CMRO2. Also, there was no correlation between CBF and CCO oxidation state. Conversely, changing oxygenation resulted in a strong correlation between the oxidation of CCO and CBF. This proves that the association between CBF and the redox state of CCO is not fixed and depends on the type of perturbation. Having a means to measure CBF and CCO oxidation state simultaneously will help understanding their contribution to intact neurovascular coupling and detecting abnormal cellular oxygen metabolism in many neurological disorders.

Keywords: Cerebral blood flow; cytochrome c oxidase; hypercapnia; neurovascular coupling; tissue oxygenation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / blood supply
  • Electron Transport Complex IV* / metabolism
  • Hypercapnia*
  • Magnetic Resonance Imaging / methods
  • Mice
  • Oxygen / metabolism

Substances

  • Electron Transport Complex IV
  • Oxygen