AAfter general anesthesia, older adults often experience cognitive deficits, especially memory loss. However, it is not clear why or how they occur. In a study published today (April 1) in PLOS biology, Researchers have taken a step towards understanding how anesthetics affect the hippocampus, a region of the brain involved in the formation and storage of memory. They tested three treatments of anesthesia in mice and found that isoflurane, an inhaled anesthetic commonly used in animal studies and sometimes in combination with other drugs in humans, had the least disruptive effect on hippocampal neurons and did not affect memory formation and consolidation.
The authors “not only examined the onset of effects and changes during the acute phase of anesthesia, but, like many studies in the past, did not study what happens after the medication is washed out,” says Beverley Orser, an anesthetist and neuroscientist at the university from Toronto, which did not participate in the study. “The results challenge a very basic notion that I think the public – and even many investigators – believe. And that means, as soon as the drugs are excreted from the body, the brain returns to its original state. And that’s not the case. “
The work began when Simon Wiegert, neuroscientist at the Center for Molecular Neurobiology Hamburg in Germany, and colleagues mapped the connections between neurons in the hippocampus to find out how individual synapses contribute to memory formation. Before the researchers carefully examine small structures in mice, they usually anesthetize the animals so that they do not move, which allows for much more precise and efficient imaging. “We wondered if this would affect the activity or the stability of the synapses themselves if we did this under anesthesia,” he says.
When the researchers scoured previously published work for clues about how patterns of activity in the brain change during anesthesia, they found that while there have been some studies looking at a particular anesthetic, there has been no systematic work on the effects of various anesthetics gave up on hippocampal activity. The team selected three popular anesthesia systems: inhaled isoflurane; a combination of the sedative medetomidine, the anti-anxiety drug midazolam, and the pain reliever fentanyl (MMF, used in animals); and ketamine and xylazine taken together, which are administered to both animals and humans. While isoflurane is often used alone in animal studies, it is usually not given by itself in humans because it can irritate the airways and cause low blood pressure in some patients.
The researchers administered each anesthetic to adult mice and then took electrophysiological records of total activity in the hippocampus. They also visualized the electrical activity of the region using calcium imaging, which provides a precise view of individual cells, but with limited temporal resolution. “So we could do this comparison of hippocampal activity using microscopy and electrophysiology, and the two techniques complement each other,” says Wiegert The scientist.
The authors found that isoflurane had the least effect on activity in the hippocampus, even when used for up to four hours. However, animals treated with either ketamine xylazine or MMF showed impaired hippocampal activity and deficits in both memory formation and consolidation – in the case of MMF, up to six hours after another drug was administered to the anesthetic antagonize and wake up the animals. The mice “wake up within a few minutes, are fairly mobile and look as if they have really recovered from the anesthesia,” explains Wiegert. “Even though the animal is awake, its brain activity is no longer the same as it was before.”
“The strongest effects of general anesthetics relate to memory systems, but these amnesic effects have been relatively little studied in the hippocampus to this level of detail,” writes George Mashour, an anesthetist and neuroscientist at the University of Michigan who was not involved in the study email to The scientist. As for the next steps, “two of the three anesthetic combinations tested in this study are primarily used in animal studies,” he adds. “Additional studies using experimental models that incorporate other anesthetic regimens commonly used in humans, including surgery, will help translate these findings into clinical care.”
“The most important [next step] it must be documented that these deficits occur [and] Understand the areas of behavior that are most vulnerable, ”says Orser. “This will help us to understand the receptors and networks involved and to develop prevention and mitigation strategies from them. At the moment there are only a few. “
W. Yang et al., “Anesthetics fragment the network activity of the hippocampus, alter the dynamics of the spine, and affect memory consolidation.” PLOS Biol, doi: 10.1371 / journal.pbio.3001146, 2021.