title: General anesthetics and cytotoxicity: possible implications for brain health.
abstract: BACKGROUND
  The search for agents that bring about faster induction and quicker recovery in the operating room have yielded numerous anesthetics whose mechanisms of action and potential toxic side effects remain unknown, especially in the young and aging brain.
  
  
  OBJECTIVE
  Taking advantage of our clinical and basic science expertise, here we subject the reader to an interesting perspective vis-à-vis the current applications of general anesthetics, and present evidence for their neurotoxic effects on the developing and elderly brains.
  
  
  RESULTS
  Recent studies have called into question the safety of general anesthetics, especially with regards to potentially significant detrimental impacts on the developing brains of young children, and cognitive decline in the elderly - often following multiple episodes of anesthesia. Despite accumulating evidence from animal studies demonstrating that general anesthesia leads to neurodegeneration and cognitive impairment, to date a clear consensus on the impact of anesthetics in humans remains elusive. Because a direct impact of anesthetics on human neuronal networks is often difficult to deduce experimentally, most laboratories have resorted to animal models - albeit with limited success in translating these findings back to the clinic. Moreover, the precise mechanisms that lead to potential cognitive, learning, and memory decline in young and elderly patients also remain to be fully defined.
  
  
  CONCLUSIONS
  This review will focus primarily on the cytotoxic effects of anesthetics, and offer some practical resolutions that may attenuate their long-term harm. An urgent need for studies on animal models and an increased focus on highly controlled prospective epidemiological studies is also reinforced.
authors.affiliation: a The Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary , Alberta , Canada.
authors.forename: Ryden
authors.initials: R
authors.lastname: Armstrong
authors.affiliation: a The Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary , Alberta , Canada.|b Department of Biology , Saint Louis University , Saint Louis , MO , USA , and.
authors.forename: Fenglian
authors.initials: F
authors.lastname: Xu
authors.affiliation: a The Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary , Alberta , Canada.
authors.forename: Anish
authors.initials: A
authors.lastname: Arora
authors.affiliation: c Pediatric Anesthesia and Pain Medicine, Alberta Children's Hospital , Calgary , Alberta , Canada.
authors.forename: Nivez
authors.initials: N
authors.lastname: Rasic
authors.affiliation: a The Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary , Calgary , Alberta , Canada.
authors.forename: Naweed I
authors.initials: NI
authors.lastname: Syed
mesh_terms: D000367:Age Factors; D000375:Aging / Q000473:pathology / Q000523:psychology; D000768:Anesthesia, General / Q000009:adverse effects* / Q000379:methods; D018681:Anesthetics, General / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D002648:Child; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000523:psychology; D006801:Humans; D007859:Learning Disabilities / Q000139:chemically induced / Q000523:psychology; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D018681:Anesthetics, General
keywords: Anesthesia; cognitive impairment; cytotoxicity; general anesthesia; pediatric anesthesia