title: The anesthetics nitrous oxide and ketamine are more neurotoxic to old than to young rat brain.
abstract: Nitrous oxide (N2O) and ketamine are common general anesthetics and antagonists of N-methyl-D-aspartate (NMDA) glutamate receptors. In clinically relevant concentrations, they induce a psychotomimetic reaction in humans and pathomorphological changes in the rat brain. We have previously shown that ketamine and N2O in combination cause the neurotoxic reaction in young adult rat brain that is apparently synergistic. Ketamine and N2O are occasionally used in geriatric anesthesia since they do not suppress cardiorespiratory function and thus are beneficial for frail elderly patients. However, in view of the evidence that N2O and ketamine have potentially serious neurotoxic effects, and that they potentiate one another's neurotoxicity, their neurotoxic potential in the aging brain needs to be evaluated. In this study we compared the neurotoxicity of ketamine and N2O, alone or in combination, in aging (18- and 24-month-old) rats and in young adult (6-month-old) rats and found that the aging brain is substantially more sensitive than the young adult brain to the neurotoxic reaction induced by either ketamine alone or the ketamine + N2O combination, but equally sensitive to the neurotoxicity induced by N2O alone.
authors.affiliation: Department of Anesthesiology, University of Virginia Health System, P.O. Box 800710, Charlottesville, VA 22908, USA. vj3w@virginia.edu
authors.forename: Vesna
authors.initials: V
authors.lastname: Jevtovic-Todorovic
authors.forename: Lisa B
authors.initials: LB
authors.lastname: Carter
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000473:pathology*; D000777:Anesthetics / Q000009:adverse effects; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D007649:Ketamine / Q000009:adverse effects*; D007928:Lethal Dose 50; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D009498:Neurotoxins / Q000009:adverse effects; D009609:Nitrous Oxide / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000777:Anesthetics; D004338:Drug Combinations; D009498:Neurotoxins; D007649:Ketamine; D009609:Nitrous Oxide