Epigenetic Mechanisms of Postoperative Cognitive Impairment Induced by Anesthesia and Neuroinflammation

Cells. 2022 Sep 21;11(19):2954. doi: 10.3390/cells11192954.


Cognitive impairment after surgery is a common problem, affects mainly the elderly, and can be divided into postoperative delirium and postoperative cognitive dysfunction. Both phenomena are accompanied by neuroinflammation; however, the precise molecular mechanisms underlying cognitive impairment after anesthesia are not yet fully understood. Anesthesiological drugs can have a longer-term influence on protein transcription, thus, epigenetics is a possible mechanism that impacts on cognitive function. Epigenetic mechanisms may be responsible for long-lasting effects and may implicate novel therapeutic approaches. Hence, we here summarize the existing literature connecting postoperative cognitive impairment to anesthesia. It becomes clear that anesthetics alter the expression of DNA and histone modifying enzymes, which, in turn, affect epigenetic markers, such as methylation, histone acetylation and histone methylation on inflammatory genes (e.g., TNF-alpha, IL-6 or IL1 beta) and genes which are responsible for neuronal development (such as brain-derived neurotrophic factor). Neuroinflammation is generally increased after anesthesia and neuronal growth decreased. All these changes can induce cognitive impairment. The inhibition of histone deacetylase especially alleviates cognitive impairment after surgery and might be a novel therapeutic option for treatment. However, further research with human subjects is necessary because most findings are from animal models.

Keywords: BDNF; DNMTs; HDACs; anesthesia; epigenetics; inflammation; neuroinflammation; postoperative cognitive dysfunction; postoperative delirium.

Publication types

  • Review

MeSH terms

  • Aged
  • Anesthesia* / adverse effects
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cognitive Dysfunction* / genetics
  • Cognitive Dysfunction* / metabolism
  • Delirium* / complications
  • Delirium* / metabolism
  • Epigenesis, Genetic
  • Hippocampus / metabolism
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Humans
  • Interleukin-6 / metabolism
  • Neuroinflammatory Diseases
  • Postoperative Cognitive Complications* / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Brain-Derived Neurotrophic Factor
  • Histones
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Histone Deacetylases

Grants and funding

This research received no external funding.