In some species, when the going gets tough, the body hits the brakes, dropping body temperature and slowing metabolism to a snail’s pace, a condition known as lethargy. Humans don’t go into a coma, but this state can be beneficial across seemingly unrelated scenarios such as intensive care unit (ICU) stays and long-distance space travel.
Researchers at Washington University in St. Louis and the University of Washington used deep brain-targeted therapeutic ultrasound to induce lethargy in mice without physically penetrating the skull. Because mice can naturally enter this floating state, the scientists also tested the technique in rats, animals that do not have insomnia in their repertoire. The survey results were published on May 25. natural metabolismmay inform studies on targeting different brain regions with ultrasound to modulate other physical activities.
The approach is noninvasive and “wonderful for many applications,” says Matteo Celli, associate professor of biomedicine and neuromotor sciences at the University of Bologna in Italy, who was not involved in the study. This seems flexible enough to act “conceptually as a thermostat,” he says, allowing the ultrasound stimulation to be adjusted as needed to change temperatures.
Clinician Michael Ambler, a researcher and lecturer studying asthenia at the Department of Physiology, Pharmacology and Neurosciences, University of Bristol, UK, believes that the use of non-invasive technology could improve asthenia for human use. It is said that it is an important step in proceeding with the introduction. work.
Some previous efforts have relied on the injection of protein genes into target regions to help activate cells under light or drug stimulation. Such an invasive approach is unlikely to be approved for human use, Ambler said, making the new study “very interesting.”
To induce numbness non-invasively, the researchers placed small helmet-like probes on rodent subjects and stimulated deep brain structures with ultrasound. The research team chose a different ultrasound frequency than those used for medical purposes such as prenatal screening. The target region is the preoptic area of the hypothalamus, which contains neurons that previous studies have suggested play a role in insomnia.
Stimulating these neurons prompts them to send signals to brown adipose tissue. Brown adipose tissue is a highly metabolizable fat located in the upper back that helps increase body temperature when it gets too cold. Ultrasound-evoked messages from the preoptic area inhibited brown fat activity in mice and prevented heat build-up. To confirm the chill, the researchers used an infrared camera to track skin cooling in areas of brown fat and heat loss in the animal’s tail. They also confirmed that the rodents’ metabolism was reduced by measuring the reduction in oxygen usage of the rodents. In addition to fat cooling and a slowed metabolism, mice exhibited other signs of lethargy, such as reduced movement and slowed heart rate.
Mice can spontaneously enter a coma when frightened or stressed. To confirm that ultrasound was causing the hypothermia, not stress or fear, the researchers turned to rats that lacked this natural response. Ultrasound signals also caused a decrease in body temperature in rats, suggesting that ultrasound to the preoptic area is responsible for the numbness.
Hong Cheng, an associate professor in the Department of Biomedical Engineering and Radiation Oncology at Washington University in St. Louis and the study’s lead author, said the effects were mild in rats. “The rat study was just a proof-of-concept that this stimulus works in non-helpless animals,” he said, adding that research still has “a long way to go.”
The researchers automated the stimulation process to keep the animals comatose. An increase in temperature triggers an ultrasonic stimulus that causes it to cool down again like a thermostat. During the experiment, the mouse was maintained in this state for 24 hours, and when the ultrasonic stimulation was turned off, normal body temperature and metabolism were rapidly restored with no apparent negative effects.
A closer look at what cells do in response to stimuli shows that ultrasound affects the flow of ions such as calcium into preoptic neurons, reaching brown fat and preventing an increase in body temperature. It turned out to be causing the signal. When the researchers removed the proteins involved in regulating this flow, the cooling effect of ultrasound diminished.
These results suggest that the protein is “something like a nanoswitch,” Chen said. She considers this finding to be the most important of her research, because similar proteins in other areas of the brain may also be sensitive to ultrasound stimulation. “If you can identify that you are sensitive to ultrasound, [proteins] In other parts of the brain, we may be regulating other behaviors,” she said, adding that we don’t yet know what that is.
The possibility of altering behavior by applying ultrasound to the brain may have ethical implications. “In the world of technology, you have to ask yourself if there is a dark side,” says Chen. “I think it’s unlikely because for this technology to work, you need a well-designed device that can precisely target specific brain regions, which is very difficult. ”
The technology will have to overcome initial skepticism. “Right now, I don’t think it’s really possible to put people into a degree of hypothermia with this technique,” Seri said, noting that there are other easier ways to make people unconscious. point out that there is
If non-invasive anesthesia induction were possible in humans, one potential use would be to buy time for stroke and heart attack patients to get to the hospital, Chen said. To tell. Both of these emergencies result in oxygen deprivation of the affected tissues, but lethargy lowers oxygen demand and may delay or prevent injury.
In the ICU, once coma is induced, many of the medications and monitoring needed for patient care may not be needed. “This study represents just the first step towards that goal,” said Professor Ambler, who studies lethargy as a way to support patients suffering from organ failure in the ICU.
Induction of coma in humans also has futuristic potential to support suspended animation when traveling through vast and lonely spaces.
Before that possibility takes off into the ambitious future, it is necessary to first conduct research on familiar Earth-limited species. Seri says the next step should be testing in larger non-human animals, possibly pigs. “They are most human-like, hairless and thermally human-like,” he says.
Mr. Cheng agrees that pigs are probably the next step on the comatose benefit ladder. “We want to take this technology step-by-step, from mice to rats to pigs to monkeys and hopefully eventually humans,” and perhaps beyond the limits of the planet.
