A team of scientists at Washington University in St. Louis have developed a non-invasive ultrasound technique to induce a torpor-like state in mammals. Torpor allows animals and birds to preserve energy and heat by dropping their body temperature and metabolic rates, enabling them to survive extreme conditions such as food scarcity and extreme cold. The technique could be used in various scenarios including spaceflight and certain patients undergoing medical procedures to conserve energy and body heat.
The multidisciplinary team, led by Associate Professor Hong Chen, induced a state of torpor in mice and rats by targeting the central nervous system with ultrasound and stimulation of the hypothalamus preoptic area in the brain. The team created a wearable ultrasound transducer, which successfully reduced the body temperature of mice by 3 degrees Celsius for about an hour, while also decreasing heart rates by 47%. Metabolism in the mice displayed a change from using both carbohydrates and fat for energy to using only fat – a key aspect of torpor.
The researchers learned that as the acoustic pressure and duration of ultrasound increases, the depth of the lower body temperature and slower metabolism (known as ultrasound-induced hypothermia and hypometabolism (UIH)) also increases. The team used a closed-loop feedback controller to maintain long-duration, stable UIH by managing ultrasound outputs. The desired body temperature was kept below 34 degrees Celsius using feedback-controlled UIH.
To learn how ultrasound-induced hypothermia and hypometabolism is activated, the team analyzed the activity of neurons in the hypothalamus preoptic area in response to ultrasound and found a consistent increase in neuronal activity in response to each ultrasound pulse. The findings revealed that UIH was stimulated by ultrasound activation of hypothalamus preoptic area neurons, which showed the critical role of this area in orchestrating a torpor-like state in mice.
Additionally, through genetic sequencing, the team discovered that ultrasound activated the TRPM2 ion channel in the hypothalamus preoptic area neurons. In a variety of experiments, the researchers confirmed that TRPM2 is an ultrasound-sensitive ion channel that contributes to the induction of UIH.
The team was also able to demonstrate that this technology could be used in a rat, which does not naturally go into torpor or hibernation. The rat showed a decrease in skin temperature, particularly in the brown adipose tissue region, as well as approximately a one-degree Celsius decrease in core body temperature, resembling natural torpor.
The multidisciplinary team included researchers from the Department of Pathology and Immunology, Psychiatry, Anesthesiology, Neuroscience, Biomedical Engineering, and Radiation Oncology at Washington University in St. Louis, with Michael R. Bruchas, a Professor of Anesthesiology and of Pharmacology at the University of Washington, also participating in the study.
Associate Professor Hong Chen explained that ultrasound stimulation has a unique capability to non-invasively target deep brain regions with high spatial and temporal precision in animal and human brains. This technology could lead to the development of a non-invasive, safe method to induce a torpor-like state for humans, which has been pursued by the scientific community for decades. The study was supported by the National Institutions of Health and the Burroughs Wellcome Fund.
