Early work on stroke repair drugs

Stroke recovery might be improved by blocking a molecule that “stops brain cells working after a stroke,” BBC News has reported.

The news comes from US research in mice that tested whether stroke recovery could be improved by blocking the action of a neurotransmitter chemical that normally inhibits the brain’s ability to repair itself. Scientists found that giving the mice a blocking drug a few days after a stroke helped them to recover movement better, but giving it too soon actually increased the damage caused by the stroke.

This study has uncovered a new mechanism that could be targeted to help the brain make a better recovery after a stroke. However, it needs to be confirmed that the processes seen in mice will also work in humans. Developing and testing a suitable drug for medical use may take a number of years and is not guaranteed to be successful.

Another important factor for limiting the damage of strokes is to learn the signs of stroke and ensure affected people are treated as soon as possible.


Where did the story come from?

The study was carried out by researchers at the University of California, Los Angeles. It was funded by a number of organisations including The Dr Miriam and Sheldon G Adelson Medical Research Foundation, the Larry L Hillblom Foundation, the Coelho Endowment, the US National Institute of Health and the US National Institute of Neurological Disorders and Stroke. The study was published in the peer-reviewed scientific journal Nature.

The story was covered by BBC News and the Daily Mail and both newspapers were clear it was a study undertaken in mice. The Daily Mail’s claim that “patients could soon benefit from drugs to overcome the disabling effects of strokes” seems premature given that the research does not confirm that the process would work in exactly the same manner in humans. Any new drug would also have to go through a number of clinical trials, which would take some years.


What kind of research was this?

This laboratory study looked at how neurotransmitters in an area of the brain may affect the ability of the brain to recovery after a stroke. To test this, the researchers gave mice drugs that reduced the concentration of a receptor in the brain a few days after they had experienced an induced stroke. The researchers then monitored the extent of their recovery of movement.

Each year 110,000 people in England have a stroke, and many of those who survive are left with debilitating brain damage. Brain damage following a stroke is the largest single cause of adult disability in the UK. Following a stroke, people will typically experience loss of movement or speech, partly due to the death of cells in the areas of the brain that control these functions but also because of the brain’s limited ability to repair itself. There are currently no drug treatments that can aid the repair of brain damage caused by stroke.


What did the research involve?

An area of the brain called the peri-infarct zone is located next to an area often affected by strokes. This region is important for brain recovery following any damage. The researchers showed that, after a stroke, the ability of this area of the brain to repair some of the damage could be inhibited by the presence of receptors for a neurotransmitter called GABA A.

The researchers took mice that had suffered a stroke and administered a drug designed to reduce the concentration of active GABA A receptors in this brain region. They also created genetically modified mice that had fewer GABA A receptors, meaning they would not be as prone to the inhibition of brain repair caused by GABA A.

The researchers assessed how well the mice recovered their ability to move by watching or videotaping them. They monitored outcomes such as the time the mice spent on each leg or the number of foot faults.


What were the basic results?

The researchers found that giving mice drugs that inhibited GABA A receptors within three days of a stroke could successfully reduce the extent to which the brain recovery mechanisms were impaired. The mice that had been treated also exhibited some degree of recovery of movement. Genetically modified mice with fewer GABA A receptors also had better recovery of physical function after stroke without being administered any drugs.

The study also found that giving the mice the drug too quickly after stroke actually increased the damage that the stroke caused. This is because GABA A receptors actually have a role to play immediately after stroke, limiting the size of the area affected. The increased damage was not seen in the genetically modified mice, which may be due to another biochemical process being able to compensate for their lack of GABA A receptors.


How did the researchers interpret the results?

The study authors say they ‘have found promising new targets for pharmacological interventions to promote recovery’ in stroke. They point out that, at present, recovery of movement after a stroke can only be aided by physical rehabilitation. They add that the findings may possibly have applications to other forms of brain injury.


Conclusion

This is a promising finding, and one that may help researchers develop new treatments and therapies for stroke patients. However, this was a laboratory study undertaken in mice and there is no guarantee that the phenomenon observed will be the same or similar in humans. If the same effect were found in humans, then any new drug or therapy would need to go through a number of stages of testing and clinical trials, which could take several years.

As well as needing to test that the drug or a variation is effective in humans, it is also crucial that we understand the timing of when to administer the drug. As the mouse study showed, giving the drug too early could actually cause more damage. It should also be noted that in this mouse model the scientists administered the drug within a few days of the stroke, so there is no indication that this discovery would be helpful to anyone who has had a stroke in the past.

Nonetheless, there is a need for new and improved ways of treating the debilitating damage that can be caused by a stroke, and this research has uncovered a promising new target for future research.
Links to the headlines

Drug 'could reduce stroke damage'. BBC News, November 4 2010
Links to the science

Clarkson AN, Huang BS, MacIsaac SE et al. Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke. Nature [advance online publication] 3 November 2010