Relevance of experimental paradigms of anesthesia induced neurotoxicity in the mouse

• Published in: PloS one 2019-03, Vol.14 (3), p.e0213543
• Main Authors: Johnson, Simon C, Pan, Amanda, Sun, Grace X, Freed, Arielle, Stokes, Julia C, Bornstein, Rebecca, Witkowski, Michael, Li, Li, Ford, Jeremy M, Howard, Christopher R A, Sedensky, Margaret M, Morgan, Philip G
• Format: Article
• Language: English
• Subjects: Analysis; Anesthesia; Anesthesiology; Anesthetics; Anesthetics, Inhalation - adverse effects; Anesthetics, Inhalation - pharmacology; Animal cognition; Animal models; Animals; Animals, Newborn; Apoptosis; Behavior, Animal - drug effects; Biology and Life Sciences; Brain damage; Brain injury; Brain research; Children & youth; Clinical trials; Cognition; Damage assessment; Defects; Disease Models, Animal; EDTA; Experiments; Exposure; General anesthesia; Halides; Haplorhini; Humans; Isoflurane; Isoflurane - adverse effects; Isoflurane - pharmacology; Learning; Medical research; Medicine and Health Sciences; Memory; Mice; Monkeys; Neonates; Neurotoxicity; Neurotoxicity syndromes; Neurotoxicity Syndromes - metabolism; Neurotoxicity Syndromes - pathology; Neurotoxicity Syndromes - physiopathology; Newborn infants; Pediatrics; Physiological aspects; Physiology; Rats; Research and Analysis Methods
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0213543

Routine general anesthesia is considered to be safe in healthy individuals. However, pre-clinical studies in mice, rats, and monkeys have repeatedly demonstrated that exposure to anesthetic agents during early post-natal periods can lead to acute neurotoxicity. More concerning, later-life defects in cognition, assessed by behavioral assays for learning and memory, have been reported. Although the potential for anesthetics to damage the neonatal brain is well-documented, the clinical significance of the pre-clinical models in which damage is induced remains quite unclear. Here, we systematically evaluate critical physiological parameters in post-natal day 7 neonatal mice exposed to 1.5% isoflurane for 2-4 hours, the most common anesthesia induced neurotoxicity paradigm in this animal model. We find that 2 or more hours of anesthesia exposure results in dramatic respiratory and metabolic changes that may limit interpretation of this paradigm to the clinical situation. Our data indicate that neonatal mouse models of AIN are not necessarily appropriate representations of human exposures.