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Study reveals how anesthetic isoflurane induces Alzheimer's-like changes in mammalian brains
Date:3/1/2012

l damage.

In a series of experiments, the investigators found that the application of isoflurane to cultured cells and mouse neurons increased the permeability of mitochondrial membranes; interfered with the balance of ions on either side of the mitochondrial membrane; reduced levels of ATP, the enzyme produced by mitochondria that powers most cellular processes; and increased levels of the cell-death enzyme caspase. The results also suggested that the first step toward isoflurane-induced cell death was increased generation of reactive oxygen species unstable oxygen-containing molecules that can damage cellular components. The performance of mice on a standard behavioral test of learning and memory declined significantly two to seven days after administration of isoflurane, compared with the results of a control group. None of the cellular or behavioral effects of isoflurane were seen when the administered agent was desflurane.

In another study by members of the same research team appearing in the February issue of Anesthesia and Analgesia and published online in November about a quarter of surgical patients receiving isoflurane showed some level of cognitive dysfunction a week after surgery, while patients receiving desflurane or spinal anesthesia had no decline in cognitive performance. That study, conducted in collaboration with investigators from Beijing Friendship Hospital in China, enrolled only 45 patients 15 in each treatment group so its results need to be confirmed in significantly larger groups.

"Approximately 8.5 million Alzheimer's disease patients worldwide will need anesthesia and surgical care every year," notes Zhongcong Xie, MD, PhD, corresponding author of both studies and director of the Geriatric Anesthesia Research Unit in the MGH Department of Anesthesia, Critical Care and Pain Medicine. "Developing guidelines for safer anesthesia care for these patients will require collaboration between specialists in
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

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