Scientists from the University of Oxford say they have discovered how the brain protects itself from damage that occurs in stroke. They wrote about their study in the journal Nature Medicine.

If we can harness this inbuilt biological mechanism, which the researchers identified in rats, we could develop effective treatments for stroke, as well as prevent other neurodegenerative diseases in the future.

Study leader, Professor Alastair Buchan, Head of the Medical Sciences Division and Dean of the Medical School at Oxford University, said: “We have shown for the first time that the brain has mechanisms that it can use to protect itself and keep brain cells alive.”

Approximately 150,000 people in the United Kingdom have a stroke each year; it is the third most common cause of death in the country.

Stroke occurs when the blood supply to a part of the brain is stopped. When this occurs, brain cells are deprived of oxygen- and nutrient-rich blood – vital for them to function properly and survive. When somebody suffers a stroke, brain cells die.

Professor Buchan said: “Time is brain, and the clock has started immediately after the onset of a stroke. Cells will start to die somewhere from minutes to at most 1 or 2 hours after the stroke.”

That is why speed is so important in stroke treatment. The faster you can get the stroke patient to hospital, the less brain damage there will be. When the patient arrives in hospital, he/she needs to be scanned and have medications administered which dissolve any clot that may be causing the block in blood flow to the brain, and get the flow re-started.

Researchers have long been trying to create neuroprotectants – medications that can buy the patient time, and help the neurons cope with damage and recover afterwards.

The team say they have identified the first example of the brain’s endogenous neuroprotection. Endogenous means “built in”.

They found the first example by going back to the mid 1920s. Researchers have known since 1926 that neurons in the part of the brain that controls memory (an area in the hippocampus) can survive oxygen deprivation, while in other areas of the hippocampus they do not survive.

Nobody has known, until now, why some neurons in the hippocampus survived while others did not when they were starved of oxygen.


Cells in some parts of the Hippocampus survive oxygen and glucose deprivation, while others do not

First author Dr Michalis Papadakis, Scientific Director of the Laboratory of Cerebral Ischaemia at Oxford University, said:

“Previous studies have focused on understanding how cells die after being depleted of oxygen and glucose. We considered a more direct approach by investigating the endogenous mechanisms that have evolved to make these cells in the hippocampus resistant.”

In animal experiments, they found that the production of hamartin helped rats’ brain cells that were being starved of oxygen and glucose survive, as might occur after a stroke. Hamartin is a type of protein.

They also demonstrated that in the other part of the hippocampus – where the brain cells die if they are starved of oxygen and glucose – there was no hamartin response.

The researchers then demonstrated that if the production of hamartin was stimulated, the neurons were more likely to be protected and survive.

Professor Buchan explained: “This is causally related to cell survival. If we block hamartin, the neurons die when blood flow is stopped. If we put hamartin back, the cells survive once more.”

They also identified the biological pathway through which hamartin acts to help the nerve cells survive the damage when they are deprived of glucose and oxygen.

The scientists pointed out that by knowing the natural biological mechanism that facilitates neuroprotection, it becomes more possible to create medications that mimic hamartin’s effect.

Professor Buchan said:

“There is a great deal of work ahead if this is to be translated into the clinic, but we now have a neuroprotective strategy for the first time. Our next steps will be to see if we can find small molecule drug candidates that mimic what hamartin does and keep brain cells alive.

While we are focussing on stroke, neuroprotective drugs may also be of interest in other conditions that see early death of brain cells including Alzheimer’s and motor neurone disease.”

Written by Christian Nordqvist