Isoflurane Preserves Spatial Working Memory in Adult Mice After Moderate Hypoxia

Abstract

Perioperative hypoxia may contribute to postoperative cognitive impairment. It is unknown, however, whether anesthetics exacerbate or protect against hypoxia-related central nervous system impairment. We sought to determine whether hypoxia alone or in combination with isoflurane disrupts working memory in mice. To this extent, we assigned adult mice to one of four treatments for 1 h: oxygen 21%, oxygen 21% + isoflurane 1.2%, oxygen 8%, or oxygen 8% + isoflurane 1.2%. Mice breathed spontaneously throughout the experiment. Body temperature was maintained at 37 degrees C + 0.5 degrees C. Mice were allowed to recover for 24 h to avoid the confounding influence of residual anesthetics on neurobehavioral performance. Working memory was assessed by use of a Y maze modified for mice. For the training trial, entry to one arm was blocked and mice were permitted to run between the two open arms for 15 min and inspect the objects outside. For the test trial, carried out 1 h later, all arms were open. Time spent in each arm was automatically recorded by a camera and associated software. Mice were tested 1, 4, and 7 days after anesthesia. A different arm was used as the novel arm for each test. Performance was analyzed with repeated-measurements analysis of variance, followed by analysis of simple main effects and by post hoc comparison using Newman-Keuls test when appropriate. P values <0.05 were considered significant. Animals subjected to hypoxia (8% oxygen for 1 h) spent significantly less time in the novel arm 1 day after the insult. The impairment, however, was transient. Hypoxic mice performance improved to the level of the control animals on the fourth post-treatment day. Mice subjected to hypoxia plus isoflurane exhibited no impairment and were comparable to the control group at all time points. Hypoxia transiently impairs performance in a spatial memory task. It appears that isoflurane protects against this deleterious effect of hypoxia.