Role of MicroRNAs in Anesthesia-Induced Neurotoxicity in Animal Models and Neuronal Cultures: a Systematic Review

  • Hisham F. Bahmad
  • Batoul Darwish
  • Karem Bou Dargham
  • Rabih Machmouchi
  • Bahaa Bou Dargham
  • Maarouf Osman
  • Zonaida Al Khechen
  • Nour El Housheimi
  • Wassim Abou-KheirEmail author
  • Farah ChamaaEmail author
Review Article


Exposure to anesthetic agents in early childhood or late intrauterine life might be associated with neurotoxicity and long-term neurocognitive decline in adulthood. This could be attributed to induction of neuroapoptosis and inhibition of neurogenesis by several mechanisms, with a pivotal role of microRNAs in this milieu. MicroRNAs are critical regulators of gene expression that are differentially expressed in response to internal and external environmental stimuli, including general anesthetics. Through this systematic review, we aimed at summarizing the current knowledge apropos of the roles and implications of deregulated microRNAs pertaining to anesthesia-induced neurotoxicity in animal models and derived neuronal cultures. OVID/Medline and PubMed databases were lastly searched on April 1st, 2019, using the Medical Subject Heading (MeSH) or Title/Abstract words (“microRNA” and “anesthesia”), to identify all published research studies on microRNAs and anesthesia. During the review process, data abstraction and methodological assessment was done by independent groups of reviewers. In total, 29 studies were recognized to be eligible and were thus involved in this systematic review. Anesthetic agents studied included sevoflurane, isoflurane, propofol, bupivacaine, and ketamine. More than 40 microRNAs were identified to have regulatory roles in anesthesia-induced neurotoxicity. This field of study still comprises several gaps that should be filled by conducting basic, clinical, and translational research in the future to decipher the exact role of microRNAs and their functions in the context of anesthesia-induced neurotoxicity.


Anesthesia Neurotoxicity MicroRNA Systematic review 



We would like to thank all members in Dr. Abou-Kheir’s Laboratory (The WAK Lab) for their help on this work. We would also like to thank the Faculty of Medicine of Beirut Arab University and the Department of Anesthesiology at Hammoud Hospital University Medical Center for their help.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12640_2019_135_MOESM1_ESM.doc (68 kb)
Online resource 1: “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) 2009 guidelines checklist (DOC 68 kb)
12640_2019_135_MOESM2_ESM.docx (16 kb)
Online resource 2: OVID/Medline and PubMed detailed search strategy (DOCX 16 kb)
12640_2019_135_MOESM3_ESM.docx (71 kb)
Online resource 3: PRISMA 2009 Flow Diagram representing the review process (DOCX 70 kb)
12640_2019_135_MOESM4_ESM.docx (45 kb)
Online resource 4: Table showing changes in microRNA expression (DOCX 45 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hisham F. Bahmad
    • 1
    • 2
  • Batoul Darwish
    • 2
  • Karem Bou Dargham
    • 1
    • 3
  • Rabih Machmouchi
    • 1
    • 3
  • Bahaa Bou Dargham
    • 1
    • 3
  • Maarouf Osman
    • 1
    • 3
  • Zonaida Al Khechen
    • 1
    • 3
  • Nour El Housheimi
    • 4
  • Wassim Abou-Kheir
    • 2
    Email author
  • Farah Chamaa
    • 2
    Email author
  1. 1.Faculty of MedicineBeirut Arab UniversityBeirutLebanon
  2. 2.Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of MedicineAmerican University of BeirutBeirutLebanon
  3. 3.Department of AnesthesiologyHammoud Hospital University Medical CenterSidonLebanon
  4. 4.Department of AnesthesiologyAmerican University of Beirut Medical CenterBeirutLebanon

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