Common anesthetic induces Alzheimer's-associated changes in mo...(a pathway leading to the generation of A...),Health

Neurologically normal mice received isoflurane for two hours at doses comparable to what would be administered to human patients. Their brains were examined 2, 6, 12 and 24 hours after they received the anesthesia and compared with the brains of control mice. Results at 6 hours showed that caspase levels were elevated and BACE had modestly increased in mice that received isoflurane. At 12 hours moderate caspase activation persisted, and BACE levels were even higher in the treated mice; and at 24 hours BACE levels were more than four times higher than in controls, and A-beta levels had also risen, while caspase activation had fallen off.

Another group of mice had been treated for seven days with the drug clioquinol before the two-hour isoflurane administration. Laboratory studies have found that clioquinol inhibits the aggregation of A-beta into neurotoxic deposits, and a clioquinol derivative is currently in clinical trials as an Alzheimer's treatment drug. Six hours after they received isoflurane, caspase levels in the clioquinol-treated mice were significantly less than in other animals that had received the anesthetic, suggesting both that A-beta aggregation contributes to a vicious cycle of further cell death echoing a finding from the team's 2007 study and that a drug like clioquinol might block isoflurane's neurotoxic effects.

"This study cannot tell us about the long-term effects of isoflurane administration; that's something we will examine in future investigations," notes Xie, who is an assistant professor of Anesthesia at Harvard Medical School (HMS) and director of the Geriatric Anesthesia Research Unit in the MGH Department of Anesthesia and Critical Care.

"Until we can directly assess the impact of isoflurane on biomarkers like A-beta levels in the plasma or cerebrospinal fluid of
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