title: Utilization of neural stem cell-derived models to study anesthesia-related toxicity and preventative approaches.
abstract: Early-life stress has been shown in both preclinical and clinical studies to cause neuroanatomical and biological alterations and disruptions in homeostasis. These alterations can lead to dysfunction in critical regulatory systems and concomitant increases in risk for the development of pathology. The existing data from research using in vivo animal models have implicated some general anesthetics as being toxic to the developing brain and causing cognitive deficits later in life. Because of obvious limitations, it is not possible to thoroughly explore the effects of early-life stress-e.g., prolonged exposure to anesthetic agents-on neurons in vivo in human infants or children. However, the availability of stem cell-derived models, especially human embryonic neural stem cells, along with their capacity for proliferation and ability to differentiate, has provided a potentially invaluable tool for examining the developmental effects of anesthetic agents in vitro. This review focuses on how embryonic neural stem cells, when combined with biochemical, pathological, and pharmacokinetic assessments, might serve as a bridging platform to provide the most expeditious approaches toward decreasing the uncertainty in extrapolating preclinical data to the human condition. This review presents key concepts in stem cell biology with respect to the nervous system, presents an overview of neural development, and summarizes the involvement of neural cell types in developmental neurotoxicity associated with anesthetic exposure.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research (NCTR)/FDA, Jefferson, AR, USA, Cheng.Wang@fda.hhs.gov.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Tucker A
authors.initials: TA
authors.lastname: Patterson
authors.forename: Merle G
authors.initials: MG
authors.lastname: Paule
authors.forename: William
authors.initials: W
authors.lastname: Slikker
mesh_terms: D000758:Anesthesia / Q000009:adverse effects*; D000818:Animals; D006801:Humans; D008954:Models, Biological; D057054:Molecular Imaging; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000517:prevention & control* / Q000628:therapy