GoKawiilA stroke can lead to a large area of dead brain tissue (black), but a drug combination could help to minimize damage by slowing brain cells’ metabolism.Credit: ZEPHYR/SPL
A combination of two well-established drugs reduces stroke-related brain damage in mice after sharply lowering the rodents’ body temperature, reports a study published today in Science Translational Medicine1. A trial of the drugs in humans with stroke showed that the therapy was safe but ineffective at the doses used.
Such drugs could one day extend the window of time for people with stroke to receive treatments that restore blood flow before too much damage is done, says Shaun Morrison, a neuroscientist at Oregon Health & Science University in Portland.
Just chilling
For decades, scientists have been interested in the use of hypothermia — drastically reducing the body’s core temperature — to lessen brain damage from various health conditions. Among them is a type of stroke that occurs when a blood clot or other obstruction blocks a blood vessel in the brain, depriving the neurons of oxygen. One theory is that inducing hypothermia during this event could decrease the metabolic activity of the neurons. This might keep the cells alive longer, giving physicians more time to try to remove or dissolve the blood clot. Hypothermia has become a standard of care for cardiac arrest, among other conditions.
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In the 1980s, researchers in China tried to induce ‘artificial hibernation’ in people with stroke using a combination of the drugs chlorpromazine and promethazine, says study co-author Yuchuan Ding, a neuroscientist at Wayne State University in Detroit, Michigan. Chlorpromazine is used to treat schizophrenia and bipolar disorder, and promethazine is used to treat nausea and vomiting after surgery. But the treatment was abandoned because the high doses used caused people’s blood pressure to become dangerously low.
The idea was “ahead of its time” and worth revisiting, Ding says. For their latest study, the researchers gave the drug combination to mice and found that it decreased their body temperature in part by causing blood vessels near the skin to dilate. This releases heat carried by blood travelling from deep within the body.
Mice treated with the two drugs consumed less oxygen than did those cooled with a different compound or with ice packs, indicating that the drugs slowed the animals’ metabolic activity. This slowing also helped to reduce body temperature.
The scientists induced stroke in some mice and found that those then given the two drugs had less dead brain tissue than did mice that did not receive the drugs. The animals also scored better on a post-stroke neurological assessment.