Molecular neurobiology
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Molecular neurobiology · Oct 2013
ReviewUtilization of neural stem cell-derived models to study anesthesia-related toxicity and preventative approaches.
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. ⋯ 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.
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Molecular neurobiology · Oct 2013
ReviewFunctional implications of an early exposure to general anesthesia: are we changing the behavior of our children?
There is a rapidly growing body of animal and clinical evidence suggesting that the exposure to anesthetics and sedatives during the critical stages of brain development results in long-lasting (perhaps permanent) impairment in cognitive development in a variety of mammalian species. With improved understanding of the mechanisms responsible for behavioral outcomes of anesthesia-induced developmental neurotoxicity, there is hope for development of protective strategies that will enable safe use of anesthesia in the youngest members of our society. Here, I review presently available evidence regarding anesthesia-induced neurocognitive and social behavioral impairments and possible strategies for preventing them. I also review limited and somewhat controversial evidence that examines the effects of nociception and surgical stimulation on anesthesia--induced developmental neurotoxicity.