title: A holistic approach to anesthesia-induced neurotoxicity and its implications for future mechanistic studies.
abstract: The year 2016 marked the 15th anniversary since anesthesia-induced developmental neurotoxicity and its resulting cognitive dysfunction were first described. Since that time, multiple scientific studies have supported these original findings and investigated possible mechanisms behind anesthesia-induced neurotoxicity. This paper reviews the existing mechanistic literature on anesthesia-induced neurotoxicity in the context of a holistic approach that emphasizes the importance of both neuronal and non-neuronal cells during early postnatal development. Sections are divided into key stages in early neural development; apoptosis, neurogenesis, migration, differentiation, synaptogenesis, gliogenesis, myelination and blood brain barrier/cerebrovasculature. In addition, the authors combine the established literature in the field of anesthesia-induced neurotoxicity with literature from other related scientific fields to speculate on the potential role of non-neuronal cells and to generate new future hypotheses for understanding anesthetic toxicity and its application to the practice of pediatric anesthesia.
authors.affiliation: University of Colorado, Anschutz Medical Campus, Department of Anesthesiology, 12801 E. 17th Ave., Mail Stop 8130, Aurora, CO 80045, United States. Electronic address: CHRISTINE.ZANGHI@UCDENVER.EDU.
authors.forename: Christine N
authors.initials: CN
authors.lastname: Zanghi
authors.affiliation: University of Colorado, Anschutz Medical Campus, Department of Anesthesiology, 12801 E. 17th Ave., Mail Stop 8130, Aurora, CO 80045, United States. Electronic address: VESNA.JEVTOVIC-TODOROVIC@UCDENVER.EDU.
authors.forename: Vesna
authors.initials: V
authors.lastname: Jevtovic-Todorovic
mesh_terms: D000777:Anesthetics / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development*; D006801:Humans; D009457:Neuroglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000209:etiology*
chemical_list: D000777:Anesthetics
keywords: Anesthesia-induced neurotoxicity; Basic science; Clinical trial; Neonate; Neuronal development; Pediatric anesthesia