Study reveals how anesthetic isoflurane induces Alzheimer's-like changes in mammalian brains

[OKIsItJustMe]

http://www.massgeneral.org/about/pressrelease.aspx?id=1443

[font face=Times, Times New Roman, Serif][font size=5]Study reveals how anesthetic isoflurane induces Alzheimer's-like changes in mammalian brains[/font]

[font size=4]MGH researchers find desflurane may be safer anesthetic option for patients with Alzheimer's disease[/font]

01/Mar/2012

[font size=3]The association of the inhaled anesthetic isoflurane with Alzheimer's-disease-like changes in mammalian brains may by caused by the drug's effects on mitochondria, the structures in which most cellular energy is produced. In a study that will appear in Annals of Neurology and has received early online release, Massachusetts General Hospital (MGH) researchers report that administration of isoflurane impaired the performance of mice on a standard test of learning and memory – a result not seen when another anesthetic, desflurane, was administered. They also found evidence that the two drugs have significantly different effects on mitochondrial function.

"These are the first results indicating that isoflurane, but not desflurane, may induce neuronal cell death and impair learning and memory by damaging mitochondria," says Yiying (Laura) Zhang, MD, a research fellow in the MGH Department of Anesthesia, Critical Care and Pain Medicine and the study's lead author. "This work needs to be confirmed in human studies, but it's looking like desflurane may be a better anesthetic to use for patients susceptible to cognitive dysfunction, such as Alzheimer's patients."

Previous studies have suggested that undergoing surgery and general anesthesia may increase the risk of Alzheimer's, and it is well known that a small but significant number of surgical patients experience a transient form of cognitive dysfunction in the postoperative period. In 2008, members of the same MGH research team showed that isoflurane induced Alzheimer's-like changes – increasing activation of enzymes involved with cell death and generation of the A-beta plaques characteristic of the disease – in the brains of mice. The current study was designed to explore the underlying mechanism and behavioral consequences of isoflurane-induced brain cell death and to compare isoflurane's effects with those of desflurane, another common anesthetic that has not been associated with neuronal 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.

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[Warpy]

1. That's a good lead on why post surgical transient dementia

has usually been a predictor of Alzheimer's later in life. Whether the anesthetic provokes or intensifies the changes is moot.