Dual Effects of Neuroprotection and Neurotoxicity By General Anesthetics On Neural Stem Cells: Role of Autophagy - Dual Effects of Neuroprotection and Neurotoxicity By General Anesthetics On Neural Stem Cells: Role of Autophagy - Open Access Pub

General anesthetics (GAs) are widely used for various essential surgical or medical procedures. Recent studies implicate the GAs has dual effects of neuroprotection and neurotoxicity on neurogenesis with unclear mechanisms. This minireview summarizes recent studies on GAs mediated effects on neurogenesis and proposed mechanisms, with focus on autophagy regulation and intracellular calcium homeostasis. DOI10.14302/issn.2574-4372.jesr-16-1380 Each year, millions of fetuses, infants and preschool children are exposed to general anesthetics (GAs) worldwide for various essential surgical or medical procedures. Unfortunately, a large number of preclinical works have demonstrated that prolonged exposure to most, if not all, general anesthetics, either volatile or intravenous, to the developing brain, can cause widespread neuronal cell death, which may be associated with long-term memory and learning disabilities.1, 2, 3 Many mechanisms have been proposed to explain GAs mediated neurotoxicity, including activation of NMDA and GABA receptors4, 5, mitochondrial damage with excessive free radicals6, 7, 8, activation of P75 growth factor9, 10, excessive inflammation11, 12, and disruption of intracellular Ca2+ homeostasis13, 14, 15. Recent studies have also suggested neurogenesis impairment may play a role, since neurotoxic effects of anesthetics occur both in vitro16, 17, 18, 19 and in vivo20, 21, 22. As methods improve, a full mechanistic understanding of neurotoxicity becomes more realistic. For example, with the development of an in vitro neurogenesis system using hESCs, induced pluripotent stem cells (iPSCs), and neural stem cells (NSCs), investigators can now study the mechanisms underlying brain development and screen the toxic effects of various anesthetics under controlled conditions (dose, number of exposures, or developmental stage). New neuroprotective strategies to avoid the anesthetics mediated toxicity, then, can be generated through neurogenesis modeling.23 Creeley et al 24reported exposure of third-trimester fetal macaque monkeys to isoflurane in utero caused widespread apoptosis of neurons and oligodendroglia critical for myelination. They use high concentrations of isoflurane, which was adjusted by painful stimulation. The volatile anesthetic concentration was titrated according to a predefined clinical endpoint that represents an intermediate surgical plane of anesthesia, where there was no motor response and only a mild sympathetic response with an increase of 10% or less in heart rate or blood pressure. Researchers achieved this endpoint via