Modeling anesthetic developmental neurotoxicity using human stem cells. Semin Cardiothorac Vasc Anesth 2013 Dec;17(4):276-87
Date
07/19/2013Pubmed ID
23859832Pubmed Central ID
PMC3830670DOI
10.1177/1089253213495923Scopus ID
2-s2.0-84887868762 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
Mounting preclinical evidence in rodents and nonhuman primates has demonstrated that prolonged exposure of developing animals to general anesthetics can induce widespread neuronal cell death followed by long-term memory and learning disabilities. In vitro experimental evidence from cultured neonatal animal neurons confirmed the in vivo findings. However, there is no direct clinical evidence of the detrimental effects of anesthetics in human fetuses, infants, or children. Development of an in vitro neurogenesis system using human stem cells has opened up avenues of research for advancing our understanding of human brain development and the issues relevant to anesthetic-induced developmental toxicity in human neuronal lineages. Recent studies from our group, as well as other groups, showed that isoflurane influences human neural stem cell proliferation and neurogenesis, whereas ketamine induces neuroapoptosis. Application of this high throughput in vitro stem cell neurogenesis approach is a major stride toward ensuring the safety of anesthetic agents in young children. This in vitro human model allows us to (1) screen the toxic effects of various anesthetics under controlled conditions during intense neuronal growth, (2) find the trigger for the anesthetic-induced catastrophic chain of toxic events, and (3) develop prevention strategies to avoid this toxic effect. In this article, we reviewed the current findings in anesthetic-induced neurotoxicity studies, specifically focusing on the in vitro human stem cell model.
Author List
Bai X, Twaroski D, Bosnjak ZJAuthor
Xiaowen Bai PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Anesthetics, GeneralAnimals
Apoptosis
Brain
Cell Death
Cell Proliferation
Child
High-Throughput Screening Assays
Humans
Infant
Models, Biological
Neurons
Neurotoxicity Syndromes
Stem Cells
Time Factors