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Commonly used anesthetic alters mouse brains

March 12, 2007 By Michael Hopkin This article courtesy of Nature News.

Study adds to concerns over drug link to Alzheimer's.

Exposure to widely used anaesthetic drugs increases production of a brain protein thought to cause Alzheimer's disease, a study of mice has shown. The research feeds concern that general anaesthesia may be linked to dementia in humans.

Inhaled doses of halothane, one of a class of drugs called volatile anaesthetics, increase the amount of a protein called amyloid beta in mouse brains, researchers at the University of Pennsylvania in Philadelphia have found.

Some 60 million people worldwide are given volatile anaesthetics each year. The drugs are known to cause 'post-operative cognitive decline' in many cases, which can last for days, weeks or years.

If these drugs boost production of amyloid beta, they may also be linked to long-term dementias such as Alzheimer's. The brains of Alzheimer's patients contain high levels of amyloid beta, although the molecule's links with disease are still unknown.

There are no data on whether the effect occurs in humans. Until such information is gathered, it will be difficult to say whether anaesthetists should stop using volatile anaesthetics, including halothane and the related isoflurane, the most widely used of the group.

Nevertheless, it adds to a growing pool of evidence that these drugs can damage the brain. "This creates a little more concern than before," says Roderic Eckenhoff, one of the researchers, who report the study in Neurobiology of Aging1. "But if you need surgery you should get your surgery."

Mouse model

Eckenhoff and his colleagues exposed mice genetically engineered to have high levels of amyloid beta and normal lab mice to halothane and isoflurane intermittently for for five days.

This creates a little more concern than before. But if you need surgery you should get your surgery.
Roderic Eckenhoff, Pennsylvania School of Medicine
The genetically engineered mice exposed to halothane had more amyloid beta, although they seemed cognitively normal. Normal mice exposed to isoflurane showed a decline in memory and learning but no increase in amyloid beta, perhaps showing that these drugs can act on the brain in more than one way.

Eckenhoff points out that the drugs might not have the same effects in humans. These mice are not expected to develop dementia from amyloid beta production, whereas humans are expected to suffer mental debilitation from the protein build-up.

Many people possess mutations that predispose them to Alzheimer's disease, although there is currently no screening for such mutations before surgery. People who are not elderly and don't have a predisposing mutation should be fine to undergo surgery, he says. "But if you had one of these mutations, even as a 20-year-old, I would be concerned," he says.

Under and out

Most general anaesthetic involves an initial injection followed by volatile anaesthetic — which can be adjusted during surgery — to keep the patient asleep. Some experts now want the procedure to use only injected drugs such as propofol. This would cost more, and would keep patients under for longer, which increases the general risks associated with going 'under'.

Last month, another research group reported that exposure to isoflurane increases amyloid beta levels in cultured brain cells (see 'Anaesthetic gas may damage brain cells'). The researchers think that volatile anaesthetics stabilize the enzymes that underpin amyloid beta production, causing the molecule to accumulate.

Doctors should gather evidence from the samples routinely collected during some brain operations, says Rudolf Tanzi of Massachusetts General Hospital in Charlestown, a member of this research group. It would take around a year to collect enough samples to see whether people taking volatile anaesthetics have more amyloid beta in their brains, he says.

Later this month, the Federal Drug Administration will meet to discuss safety issues surrounding a range of anaesthetics. It is too early to ban isoflurane, says Tanzi.

Nevertheless, he says that early data suggest that not all volatile anaesthetics have the same brain effects as isoflurane. "Our data indicate that desflurane is safer," he says.


  1. Bianchi S. L., et al. Neurobiol. Aging, doi:10.1016/j.neurobiolaging.2007.02.009 (2007).


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