Brain changes due to hypoxia during light anaesthesia can be prevented by deepening anaesthesia; a study in rats

PLoS One. 2018 Feb 16;13(2):e0193062. doi: 10.1371/journal.pone.0193062. eCollection 2018.


In anaesthetic practice the risk of cerebral ischemic/hypoxic damage is thought to be attenuated by deep anaesthesia. The rationale is that deeper anaesthesia reduces cerebral oxygen demand more than light anaesthesia, thereby increasing the tolerance to ischemia or hypoxia. However, evidence to support this is scarce. We thus investigated the influence of light versus deep anaesthesia on the responses of rat brains to a period of hypoxia. In the first experiment we exposed adult male Wistar rats to deep or light propofol anaesthesia and then performed [18F]- Fludeoxyglucose (FDG) Positron Emission Tomography (PET) scans to verify the extent of cerebral metabolic suppression. In subsequent experiments, rats were subjected to light/deep propofol anaesthesia and then exposed to a period of hypoxia or ongoing normoxia (n = 9-11 per group). A further 5 rats, not exposed to anaesthesia or hypoxia, served as controls. Four days later a Novel Object Recognition (NOR) test was performed to assess mood and cognition. After another 4 days, the animals were sacrificed for later immunohistochemical analyses of neurogenesis/neuroplasticity (Doublecortin; DCX), Brain Derived Neurotrophic Factor (BDNF) expression and neuroinflammation (Ionized calcium-binding adaptor protein-1; Iba-1) in hippocampal and piriform cortex slices. The hippocampi of rats subjected to hypoxia during light anaesthesia showed lower DCX positivity, and therefore lower neurogenesis, but higher BDNF levels and microglia hyper-ramification. Exploration was reduced, but no significant effect on NOR was observed. In the piriform cortex, higher DCX positivity was observed, associated with neuroplasticity. All these effects were attenuated by deep anaesthesia. Deepening anaesthesia attenuated the brain changes associated with hypoxia. Hypoxia during light anaesthesia had a prolonged effect on the brain, but no impairment in cognitive function was observed. Although reduced hippocampal neurogenesis may be considered unfavourable, higher BDNF expression, associated with microglia hyper-ramification may suggest activation of repair mechanisms. Increased neuroplasticity observed in the piriform cortex supports this, and might reflect a prolonged state of alertness rather than damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthesia / adverse effects*
  • Animals
  • Brain / diagnostic imaging
  • Brain / pathology*
  • Doublecortin Protein
  • Hypoxia / complications*
  • Hypoxia / etiology
  • Hypoxia-Ischemia, Brain / diagnostic imaging
  • Hypoxia-Ischemia, Brain / etiology
  • Hypoxia-Ischemia, Brain / prevention & control*
  • Male
  • Positron-Emission Tomography
  • Rats
  • Rats, Wistar

Grants and funding

The study qualified for the Young Investigator Grant from the Dutch association of anaesthesiology (Nederlandse verenining voor anesthesiologie to AFK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.