September 23, 2014

Weill Cornell Study Shows Anesthesia May Not Cause Long-Term Damage As Thought

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A recent study out of Weill Cornell Medical College has found that a commonly-used general anesthetic may not have negative long-term effects on children and the elderly as previously thought.

Led by Jimcy Platholi, a researcher and instructor of pharmacology in anesthesiology, and Prof. Hugh Hemmings, anesthesiology, the study provides new information about the effects of isoflurane, a common inhalation anesthetic used in surgical practices.

It has been suspected that the use of anesthetics in both infants and the elderly can be detrimental due to the effects that anesthesia can have on the connections between neurons.

“Recently, concerns have arisen that anesthetic exposure early in childhood might irreversibly affect brain development during a critical period by altering synaptic plasticity and increasing brain cell death,” Hemmings said. “And that anesthetic exposure in the elderly might lead to long-term cognitive deficits.”

According to Hemmings, infants’ neurons are still developing, and neurons in the elderly are slower to regenerate, making both groups more susceptible to cognitive changes caused by anesthesia. Isoflurane is commonly used as a general anesthetic, or part of a cocktail of different anesthetics used during major surgeries. The complete picture of how exactly isoflurane works is still being pieced together, Hemmings said. Though it is being replaced by other anesthetics for treatment in humans, isoflurane is still widely used in veterinary medicine.

Post-surgical cognitive effects, even in adults, have been commonly observed, though in most cases the effects are not severe and any effects disappear within a reasonable time frame, Hemmings said.

Anesthesia will remain in the body and continue to exert an effect as long as its concentration is high enough. However, such effects have not been proven to be directly caused by anesthetics alone. Painkillers are often used after major surgeries to relieve any lingering pain and may have an effect on cognition.

In addition, the anesthetic may still be present in the body even after its effects have worn off, Hemmings said. As such, when anesthesia is combined with painkillers and stress, patients can experience detrimental cognitive effects post-surgery.

According to Hemmings, the use of anesthetics in modern medicine is unavoidable, so it is necessary to fully understand any potential negative effects the drugs could have on the brain and its connections in the long term. There are some ongoing clinical studies hoping to shed more light on both the short and long-term cognitive effects of anesthetics in adult and developing brains.

As part of the study led by Platholi and Hemmings, researchers used neurons from young mice in order to study the short and long-term effects of isoflurane.

“We used hippocampal cell cultures from embryonic day 18 mice that are grown in vitro for three weeks in order to study mature, established synapses,” Platholi said.

Hippocampal cells were studied because they are known to be responsible for converting short-term memory to long-term memory as well as encoding new memories, Platholi said.

After exposure to isoflurane, the mouse neurons showed reduced number and volume of dendritic spines. However, spines regrew once the culture was no longer exposed to isoflurane, according to Hemmings.

Dendritic spines serve as connection points between neurons and are important for memory and learning. They are considered to be plastic and will change in both number and specific connections throughout a human’s normal lifespan, according to Hemmings.

In early development, dendritic spines are eliminated and regrown at a high rate, according to Hemmings. This turnover rate stabilizes once adulthood is reached.

Courtesy of Jimcy PlatholiNifty neurons | This image shows dendrites, the signal-transporting parts of neurons, in green and dendritic spines in yellow. Dendritic spines serve as the contact points between dendrites and allow signals to travel between neurons. A recent study from Weill Cornell Medical College showed that while the general anesthetic isoflurane reduces the number of dendritic spines, once the anesthetic wears off the spines do return, indicating that the cognitive changes caused by isoflurane may be only temporary.