As pediatric specialists become increasingly aware that surgical anesthesia may have lasting effects on the developing brains of young children, new research suggests the threat may also apply to adult brains.
Everyone knows that there are risks involved with undergoing surgery, but according to a new study, anesthesia may cause some people to lose their memory.
In the years past, some researchers who wanted to examine whether changes occurred not only in immature, developing cells of kids’ brains, but also in the mature cells of adult brains. To test if these changes actually occurred, they injected newborn, juvenile, and adult mice with an anesthetic called isoflurane and found that it was toxic to a cell that help control memory and learning, called dentate gyrus, according to Everyday Health.
Also Researchers from Cincinnati Children’s Hospital Medical Center report June 5 the Annals of Neurology that testing in laboratory mice shows anesthesia’s neurotoxic effects depend on the age of brain neurons — not the age of the animal undergoing anesthesia, as once thought.
Although more research is needed to confirm the study’s relevance to humans, the study suggests possible health implications for millions of children and adults who undergo surgical anesthesia annually, according to Andreas Loepke, MD, PhD, a physician and researcher in the Department of Anesthesiology.
“We demonstrate that anesthesia-induced cell death in neurons is not limited to the immature brain, as previously believed,” said Loepke. “Instead, vulnerability seems to target neurons of a certain age and maturational stage. This finding brings us a step closer to understanding the phenomenon’s underlying mechanism”
According to the experts, new neurons are generated abundantly in most regions of the very young brain, explaining why previous research has focused on that developmental stage. In a mature brain, neuron formation slows considerably, but extends into later life in dentate gyrus and olfactory bulb.
Researchers exposed newborn, juvenile and young adult mice to a widely used anesthetic called isoflurane in doses approximating those used in surgical practice. Newborn mice exhibited widespread neuronal loss in forebrain structures — confirming previous research — with no significant impact on the dentate gyrus. However, the effect in juvenile mice was reversed, with minimal neuronal impact in the forebrain regions and significant cell death in the dentate gyrus.
Explaining further, the researchers said:”We demonstrate that anesthesia-induced cell death in neurons is not limited to the immature brain, as previously believed,” Andreas Loepke, study author and researcher in the department of anesthesiology at Cincinnati Children’s Hospital Medical Center, said. “Instead, vulnerability seems to target neurons of a certain age and maturational stage. This finding brings us a step closer to understanding the phenomenon’s underlying mechanism.”
“We found something very interesting, in that cell death occurred in the spot where the dentate gyrus forms new neurons,”
The researchers say more research is necessary in order to find the root cause and impact of anesthesia-related cell death.
“During development, we form twice as many neurons as we need as an adult. The brain needs to be pruned back to properly function,” Loepke said. “So it’s currently unknown whether anesthesia kills neurons that would have been eliminated anyways from the brain or neurons later needed for vital function.”
Although these findings occurred in mice, experts believe the effect is likely to be the same in humans.
Doctors already told patients that there may be small changes in their mental capacity after surgery, but the chances are small only eight percent of patients have mental problems three months later, according to Dr. Jeffrey Silverstein, professor of anesthesiology, Surgery and Geriatrics and Palliative Medicine at the Icahn School of Medicine at Mount Sinai in New York City.
“Research shows that if you’re exposed to these agents during the time neurons are growing, it disrupts their development,” Dr. Silverstein revealed. “But this is the first paper indicting that this happens in adults.”
They said these findings could have also contributed to the effects of anesthesia on older people from another study, which found that general anesthesia can increase the risk of dementia and the development of neurodegenerative disorders, such as Parkinson’s and Alzheimer’s disease.
They associated the initial decline in cognitive function, known as postoperative cognitive dysfunction, POCD, with promoting neuroinflammatory reactions in the brain, causing the brain’s cells to degenerate.
The researchers concluded that preoperative evaluations should be taken of the elderly before administering anesthesia, however, based on the evidence from Loepke’s study, doctors may want to consider these steps for people of all ages.
“You can’t section a human brain,” Loepke said, “But if it were occurring in humans, we would predict that anesthetics affect neurons in patients of all ages.”
The team then performed extensive studies to discover that age and maturational stage of the affected neurons were the defining characteristics for vulnerability to anesthesia-induced neuronal cell death. The researchers observed similar results in young adult mice as well.
Another surprising finding is that the sleep-inducing drug zolpidem (Ambien) may help minimally conscious brain-injured patients to recover some functions. This paradox is due to a common phenomenon in which patients in the first stage of anesthesia may move around or vocalize, due to stimulation of the thalamus.
According to Managing Director, of Massachusetts general hospital, Emmery Brown, Anesthesiologists know how to safely maintain their patients in the deepest states of general anesthesia, but most are not familiar with the basic neural circuit mechanisms that allow them to carry out their life-sustaining work.”
“Anesthesia hasn’t been attacked as seriously as other questions in neuroscience,” he adds. “Why shouldn’t we be doing the same thing for questions of general anesthesia?”
Andreas Loepke, MD, at the University of Cincinnati College of Medicine, agrees. “Anesthetics are very powerful medications with a very narrow safety margin, as evidenced by the unfortunate events surrounding Michael Jackson’s death,” he says.
“These medications carry potent side effects, such as respiratory depression, loss of protective airway reflexes, blood-pressure instability, as well as nausea and vomiting.”
He concludes that a better understanding of how general anesthesia works at the cellular and molecular level could aid the development of anesthetic drugs that lack those side effects.