Drug-induced hypometabolism may slow stroke-related brain damage, according to early research involving animals and people.
The experimental treatment uses two existing medicines to reduce metabolism and create a state resembling hypothermia.
Tests in mice and rhesus monkeys found that the approach protected brain tissue, while an early trial involving 32 stroke patients reported no notable side effects.
The treatment combined chlorpromazine, an antipsychotic medicine, with the sedative promethazine. The combination was known as C+P.
The small human trial found no significant improvements in the amount of brain damage or participants’ ability to carry out daily activities independently.
Further studies will be needed to establish what benefits the treatment might offer people who have experienced strokes.
The research also provided more information about the role of hypometabolism, when the body uses less energy, in the protective effects associated with hypothermia.
Dr Eric Landsness, assistant professor of neurology at Washington University School of Medicine in St Louis, was not involved in the research.
He said: “What’s exciting about this study is that it’s clear that it’s not just the hypothermia, but it’s the hypometabolism.”
The researchers tested C+P as a treatment for acute ischaemic stroke, which occurs when blood flow to the brain is suddenly blocked.
Ischaemic strokes account for more than 85 per cent of strokes. The acute form is a medical emergency involving the sudden loss of blood flow and neurological function.
Restoring blood flow through reperfusion treatment can cause further damage through processes that began while the brain was deprived of blood.
Dr Patrick Lyden, professor of physiology and neuroscience, neurology and neurosurgery at the University of Southern California Keck School of Medicine, was not involved in the study.
He said: “You can get significant injury from a lot of processes that were set in motion during the ischaemia.”
Researchers have previously examined whether hypothermia could protect brain tissue from damage caused by both ischaemia and the return of blood flow.
Lyden described hypothermia as “one of the most powerful ways of protecting the brain that we’ve ever studied in lab animals”.
He added: “It’s the standard by which all other brain protectants are measured.”
Hypothermia occurs when body temperature falls below 35°C.
Under normal circumstances, it can be dangerous because the cold may slow the heart and nervous system enough to cause cardiac and respiratory failure.
One theory behind its therapeutic effects is that cooling slows metabolism in a similar way to hibernation.
Lyden said slowing metabolism could also delay the process of brain-cell death.
Therapeutic hypothermia can protect the brain following cardiac arrest and is sometimes used to treat newborn babies with hypoxic-ischaemic encephalopathy.
This is a brain injury caused by reduced oxygen and blood flow around the time of birth.
However, studies of hypothermia in adults who have experienced strokes have produced less encouraging results.
The researchers suggested C+P might provide a more effective way to slow metabolism in stroke patients.
Earlier experiments found that the combination reduced inflammation in the nervous system in rodent stroke models, possibly through metabolic changes that were independent of hypothermia.
In the new study, researchers compared C+P with two other ways of lowering body temperature in mice: adenosine 5’-monophosphate and surface cooling using cold water and ice packs.
All three approaches caused hypothermia, but only C+P reduced overall oxygen consumption and energy expenditure, two signs of slower metabolism.
Landsness said the findings suggested metabolism was more than a secondary effect of hypothermia and should be studied in its own right.
In mice, C+P reduced the burning of sugar by the brain and brown fat, tissue that burns fuel to produce heat.
The treatment was also linked to less brain tissue damage and lower lactate accumulation after stroke. Lactate can build up and contribute to cell death.
Similar effects were observed in rhesus monkeys treated with C+P.
The small human trial suggested that the metabolic effects could also occur in people.
Patients given the highest dose had lower levels of metabolism-related proteins in their blood.
They were also the only participants to experience a significant fall in body temperature four hours after treatment, although their temperatures did not reach the level defined as hypothermia.
Temperatures did fall to that level in the mice and monkeys.
The participants also received standard treatments to restore blood flow to the brain.
C+P did not reduce the amount of brain damage detected 72 hours after treatment or improve independence in daily activities after 90 days.
The study authors, based at Capital Medical University in Beijing, did not respond to a request for comment.
They said future trials could establish whether C+P protects the brain following a stroke.
Although the treatment caused no notable side effects in the early human trial, Lyden said the medicines could potentially interact and cause muscle spasms, seizures or changes in heart rhythm.
He suggested that researchers may need to find other medicines capable of slowing metabolism without these potential risks.
Landsness said: “The new paper happened to fall upon a drug [combo] that happens to induce hypothermia and hypometabolism, but we don’t necessarily know why.”
Further research will be needed to understand how the drugs produce these effects.
Landsness’s laboratory is studying the neural circuits involved in hypothermia and hypometabolism, which could identify other targets for treatment.
