title: Bioenergetic homeostasis decides neuroprotection or neurotoxicity induced by volatile anesthetics: a uniform mechanism of dual effects.
abstract: The commonly used volatile anesthetic isoflurane or sevoflurane has been shown to be both neuroprotective and neurotoxic in various cell cultures and animal models. Some possible mechanisms have been raised to elucidate volatile anesthetics-induced neuroprotection or neurotoxicity, respectively. However, none of these can reconcile the linkage between their dual effects. Similar to volatile anesthetics, some drugs and nonpharmacological factors also can produce neuroprotection and neurotoxicity, which is associated with bioenergetic metabolism of neuronal cells. Here we present a uniform mechanism, bioenergetic homeostasis hypothesis, to explain neuroprotection and neurotoxicity induced by volatile anesthetics. The numerous evidences have shown that volatile anesthetics could affect mitochondrial electron transport complexes and glycolysis related pathways in cells, which could alter intracellular calcium homeostasis, ROS production and adenosine triphosphate (ATP) synthesis. Duration and concentration of exposure to volatile anesthetics could play a role on severity of bioenergy inhibition. Mild bioenergetic metabolism inhibition trigger signaling events involving preconditioning on neurons, and further bioenergy impairment could lead to neuronal cellular apoptosis, inhibition of neurogenesis and elevated β-Secretase, which drive pathogenesis of neurodegeneration.
authors.affiliation: Department of Anesthesiology, Huashan Hospital, Fudan University, No. 12, Urumqi Central Rd., Shanghai 200040, PR China. snapzhang@yahoo.com.cn
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Hui
authors.initials: H
authors.lastname: Qiao
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D018685:Anesthetics, Inhalation / Q000494:pharmacology* / Q000633:toxicity; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D006019:Glycolysis / Q000187:drug effects; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008959:Models, Neurological; D055495:Neurogenesis / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D055549:Volatile Organic Compounds / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D018685:Anesthetics, Inhalation; D045222:Electron Transport Chain Complex Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D055549:Volatile Organic Compounds; D000255:Adenosine Triphosphate