Xenon pretreatment may prevent early memory decline after isoflurane anesthesia and surgery in mice

Postoperative cognitive decline (POCD) is a common complication following surgery, but its aetiology remains unclear. We hypothesized that xenon pretreatment prevents POCD by suppressing the systemic inflammatory response or through an associated protective signaling pathway involving heat shock protein 72 (Hsp72) and PI3-kinase. Twenty-four hours after establishing long-term memory using fear conditioning training, C57BL/6 adult male mice (n = 12/group) received one of the following treatments: 1) no treatment group (control); 2) 1.8% isoflurane anesthesia; 3) 70% xenon anesthesia; 4) 1.8% isoflurane anesthesia with surgery of the right hind leg tibia that was pinned and fractured; or 5) pretreatment with 70% xenon for 20 minutes followed immediately by 1.8% isoflurane anesthesia with the surgery described above. Assessments of hippocampal-dependent memory were performed on days 1 and 7 after treatment. Hsp72 and PI3-kinase in hippocampus, and plasma IL-1β, were measured using western blotting and ELISA respectively, from different cohorts on day 1 after surgery. Isoflurane induced memory deficit after surgery was attenuated by xenon pretreatment. Xenon pretreatment prevented the memory deficit typically seen on day 1 (P = 0.04) but not on day 7 (P = 0.69) after surgery under isoflurane anesthesia, when compared with animals that underwent surgery without pretreatment. Xenon pretreatment modulated the expression of Hsp72 (P = 0.054) but had no significant effect on PI3-kinase (P = 0.54), when compared to control. Xenon pretreatment also reduced the plasma level increase of IL-1β induced by surgery (P = 0.028). Our data indicated that surgery and/or Isoflurane induced memory deficit was attenuated by xenon pretreatment. This was associated with a reduction in the plasma level of IL-1β and an upregulation of Hsp72 in the hippocampus.