title: Lithium Protects Against Anaesthesia Neurotoxicity In The Infant Primate Brain.
abstract: Exposure of infant animals, including non-human primates (NHPs), to anaesthetic drugs causes apoptotic death of neurons and oligodendrocytes (oligos) and results in long-term neurodevelopmental impairment (NDI). Moreover, retrospective clinical studies document an association between anaesthesia exposure of human infants and significant increase in NDI. These findings pose a potentially serious dilemma because millions of human infants are exposed to anaesthetic drugs every year as part of routine medical care. Lithium (Li) at clinically established doses is neuroprotective in various cerebral injury models. We therefore investigated whether Li also protects against anaesthesia neurotoxicity in infant NHPs. On postnatal day 6 NHPs were anaesthetized with the widely used anaesthetic isoflurane (ISO) for 5 h employing the same standards as in a human pediatric surgery setting. Co-administration of Li completely prevented the acute ISO-induced neuroapoptosis and significantly reduced ISO-induced apoptosis of oligodendroglia. Our findings are highly encouraging as they suggest that a relatively simple pharmacological manipulation might protect the developing primate brain against the neurotoxic action of anaesthetic drugs while not interfering with the beneficial actions of these drugs. Further research is needed to determine Li's potential to prevent long-term NDI resulting from ISO anaesthesia, and to establish its safety in human infants.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, US.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Noguchi
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, US.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Johnson
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, US.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Kristich
authors.affiliation: Division of Comparative Medicine, Oregon National Primate Research Center, Oregon Health &Science University, Beaverton, Oregon, US.
authors.forename: Lauren D
authors.initials: LD
authors.lastname: Martin
authors.affiliation: Division of Neuroscience, Oregon National Primate Research Center, Oregon Health &Science University, Beaverton, Oregon, US.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Dissen
authors.affiliation: Department of Anesthesiology &Perioperative Medicine, Oregon Health &Science University, Portland, Oregon, US.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Olsen
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, US.
authors.forename: John W
authors.initials: JW
authors.lastname: Olney
authors.affiliation: Department of Anesthesiology &Perioperative Medicine, Oregon Health &Science University, Portland, Oregon, US.
authors.forename: Ansgar M
authors.initials: AM
authors.lastname: Brambrink
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D007530:Isoflurane / Q000633:toxicity*; D008094:Lithium / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008253:Macaca mulatta; D065886:Neurodevelopmental Disorders / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology
chemical_list: D018685:Anesthetics, Inhalation; D018696:Neuroprotective Agents; D008094:Lithium; D007530:Isoflurane