Sedation agents differentially modulate cortical and subcortical blood oxygenation: evidence from ultra-high field MRI at 17.2 T

PLoS One. 2014 Jul 22;9(7):e100323. doi: 10.1371/journal.pone.0100323. eCollection 2014.

Abstract

Background: Sedation agents affect brain hemodynamic and metabolism leading to specific modifications of the cerebral blood oxygenation level. We previously demonstrated that ultra-high field (UHF) MRI detects changes in cortical blood oxygenation following the administration of sedation drugs commonly used in animal research. Here we applied the UHF-MRI method to study clinically relevant sedation drugs for their effects on cortical and subcortical (thalamus, striatum) oxygenation levels.

Methods: We acquired T2*-weighted images of Sprague-Dawley rat brains at 17.2T in vivo. During each MRI session, rats were first anesthetized with isoflurane, then with a second sedative agent (sevoflurane, propofol, midazolam, medetomidine or ketamine-xylazine) after stopping isoflurane. We computed a T2*-oxygenation-ratio that aimed at estimating cerebral blood oxygenation level for each sedative agent in each region of interest: cortex, hippocampus, thalamus and striatum.

Results: The T2*-oxygenation-ratio was consistent across scan sessions. This ratio was higher with inhalational agents than with intravenous agents. Under sevoflurane and medetomidine, T2*-oxygenation-ratio was homogenous across the brain regions. Intravenous agents (except medetomidine) induced a T2*-oxygenation-ratio imbalance between cortex and subcortical regions: T2*-oxygenation-ratio was higher in the cortex than the subcortical areas under ketamine-xylazine; T2*-oxygenation-ratio was higher in subcortical regions than in the cortex under propofol or midazolam.

Conclusion: Preclinical UHF MRI is a powerful method to monitor the changes in cerebral blood oxygenation level induced by sedative agents across brain structures. This approach also allows for a classification of sedative agents based on their differential effects on cerebral blood oxygenation level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / drug effects*
  • Hypnotics and Sedatives / pharmacology*
  • Ketamine / pharmacology
  • Magnetic Resonance Imaging / methods
  • Male
  • Medetomidine / pharmacology
  • Methyl Ethers / pharmacology
  • Midazolam / pharmacology
  • Oxygen / blood*
  • Propofol / pharmacology
  • Rats, Sprague-Dawley
  • Sevoflurane
  • Xylazine / pharmacology

Substances

  • Hypnotics and Sedatives
  • Methyl Ethers
  • Xylazine
  • Sevoflurane
  • Ketamine
  • Medetomidine
  • Midazolam
  • Oxygen
  • Propofol

Grants and funding

This work was supported by the Inserm Avenir program and the French National Research Agency (ANR) through grant ANR-08-PCVI-0009-01. LU is funded by a senior grant of the European Research Council (NeuroConsc Program). LU and BJ are supported by the Inserm Avenir program and the Fondation Bettencourt Schueller. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.