Our body loves the state of homeostasis, where everything is in perfect equilibrium, from temperature to pH levels to fluid balance. As soon as the body’s core temperature drops below 95°F (35°C) and stays there for a long time, the heart, nervous system and other organs start to function poorly, which makes hypothermia extremely dangerous when not dealt with immediately. It is a medical emergency that can result in loss of consciousness or death.
Researchers have now found a way to turn this emergency into a tool to protect the body from the devastating effects of another health emergency—a stroke. A recent study investigated whether drugs like chlorpromazine and promethazine (C+P) can be used to mimic the chilling effects of hypothermia to protect the brain from the aftereffects of stroke.
C+P treatment reduced brain damage and improved neurological function in a mouse stroke model. In rhesus monkeys, the drugs lowered body temperature, which suppressed the metabolic rate and protected the brain from stroke-related injury.
The researchers then moved to a small Phase I clinical trial with 32 stroke patients. The treatment was safe at a 100 mg dose and successfully lowered body temperature while slowing the body’s energy use, an effect that the researchers suggest helps protect the brain after a stroke.
The findings were published in Science Translational Medicine.
A search for brain protection
Acute ischemic stroke (AIS) is one of the leading causes of death and long-term disability worldwide. It can have lasting effects on both the body and mind. Survivors may struggle with speaking, moving, remembering things or performing everyday tasks, often requiring months of rehabilitation to regain lost abilities and restore their quality of life.
Currently, doctors treat strokes by using drugs or surgery to remove blood clots and restore blood flow. However, even when blood flow is restored, the brain often continues to suffer damage from the initial injury.
In this study, the researchers wanted to explore an alternative and effective way to protect the brain immediately after a person has a stroke. The researchers took a three-step approach to investigate whether a drug combination called C+P could place the brain into a protective, hibernation-like state after a stroke.
What happened in mice
They first tested the treatment in mice, creating a temporary blockage in a brain artery to mimic a stroke before administering the drugs. To understand how the treatment worked under different conditions, the mice were housed in cold, normal or warm environments.
The researchers then measured oxygen consumption to see how much energy the body was using and used advanced brain scans to track chemical changes linked to brain health. The drugs successfully lowered the mice’s body temperature and slowed their metabolism.
Unlike traditional cooling methods such as ice, which cause mice to huddle and shiver, C+P lowered body temperature without triggering shivering. In mice that had a stroke, the treatment reduced the size of the brain injury and improved neurological recovery.
Results carried into primates
Next, the treatment was tested on rhesus monkeys. After inducing stroke-like conditions, the researchers administered C+P intravenously.
The treatment safely lowered the monkeys’ core body temperature to around 33–34°C (91.4–93.2°F) and shifted the metabolism from glucose to fats and ketones; a similar change was also observed in the mice. Monkeys treated with C+P after a stroke developed significantly smaller brain injuries than those that did not receive the treatment.
Early signals in patients
The team then tested whether the treatment was safe for humans by running a small trial with 32 stroke patients who were randomly given either the drug or a placebo. Those receiving the drug received one of four doses—10, 20, 50 or 100 mg—while their blood pressure, heart rate and other vital signs were closely monitored. They were followed for 90 days to check for any long-term complications.
They found that the treatment was safe and well tolerated, with no dangerous drops in blood pressure or breathing complications. While the lower doses made no real difference, the 100 mg dose successfully triggered a mild drop in temperature and slowed the metabolism. All of the patients who received the highest dose showed good recovery after 90 days.
The researchers believe the findings show promising potential for translating C+P treatment into clinical practice and say larger trials are now needed to further evaluate its safety and effectiveness.
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Publication details
Shuaili Xu et al, The translational potential of drug-induced hypothermia in acute ischemic stroke, Science Translational Medicine (2026). DOI: 10.1126/scitranslmed.ady7847
Journal information:
Science Translational Medicine
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