Chilling the body with drugs could limit brain damage from stroke

The core body temperature of mice and monkeys was effectively reduced using a combination of two drugs typically used for hay fever and psychosis, leading to decreased brain damage following a stroke. These drugs have undergone initial testing in humans and are set to be assessed in a subsequent clinical trial.

Over the years, researchers have explored methods to cool the brain after a stroke to minimize damage. The aim is to place brain cells in a state akin to hibernation, reducing their need for oxygen and glucose when blood supply is interrupted. Keeping brain cells alive until blood flow resumes, such as by removing a clot, could prevent significant brain damage and associated speech and movement disorders.

However, attempts using physical cooling methods like blankets, ice packs, and helmets have failed due to severe discomfort and uncontrollable shivering, according to Kirsten Coupland from the University of Newcastle in Australia, who was not part of the study.

Shivering is a natural response the body uses to counteract hypothermia, making it difficult to lower the body temperature sufficiently, Coupland explains. “It’s encouraging to see various cooling therapies being trialed for stroke, as physical cooling is impractical,” she adds.

Shuaili Xu and his team at Capital Medical University in Beijing, China, administered promethazine and chlorpromazine—known to lower body temperature since the 1950s—to mice and rhesus monkeys after induced strokes.

In both species, the drug combination led to decreased core body temperature, reduced glucose metabolism in cells, and less brain damage from the stroke. The monkeys treated with the drugs also showed improved limb use.

Following this, the researchers conducted a clinical trial with 32 recent stroke patients. Upon hospital admission, participants received either the drug combination or a placebo, alongside standard clot-removal treatment.

The drug treatment only lowered patients’ body temperature by 0.3°C (approximately 0.5°F) and did not reduce stroke damage. Xu suggests this is because the 12-hour infusion period was too slow to significantly lower core body temperature, possibly resulting in low blood drug concentration per time unit.

The team is planning another trial to determine if quicker infusions over one hour could achieve better cooling effects and therapeutic outcomes. “Given the safety profile and existing use of these drugs for other conditions, further clinical trials are justified,” Coupland states.

Promethazine and chlorpromazine have long been considered relatively safe. Promethazine, a sedating antihistamine, helps with hay fever and sleep, while chlorpromazine is used for schizophrenia and bipolar disorder management. Both drugs act on the central nervous system to lower core body temperature without causing shivering or feelings of coldness.