Current Research

The critical first ten days
It is now clear that outcome from a brain "injury" - whether this is from true, traumatic impact to the head, or from a stroke or bleeding in the brain - is influenced heavily not only by the severity of the initial event, but also by adverse changes in the brain that occur in the ten days after the event. These changes develop while the patient is in hospital, so that there is a chance for specialists to try to influence the situation for the better. To do this, we first need to understand the processes that are under way, and this is HeadFirst's main goal.

What have we achieved so far?
Understanding "spreading depression"

This phenomenon in the grey matter of the brain has nothing to do with the sort of depression that we all know about. Instead, it is the term first used by a Brazilian researcher, Aristides Leão (pronounced Leon - Portuguese for "lion") who became famous for discovering it - a depression of normal brain wave activity that spreads out gradually across the brain surface from the point where it starts. Rather like the ripples that spread in a pond when a stone is dropped into it.

When the first ripple reaches a new point in the brain, the effects are very profound. All nerve cells and all their supporting cells (the astrocytes or "star cells") lose their normal electrical charge (the technical term is "depolarisation"). Every cell - nerve cell or astrocyte - can be thought of like a battery: depolarisation short-circuits it, and it has then to be recharged- requiring delivery of extra glucose and oxygen through an increase in blood supply to the area affected by the spreading depression. Re-charging is essential, not only to allow a cell in the brain to resume its normal function, but also for it to remain alive.

So spreading depression sounds like a real threat to the survival of nerve cells, but most often it is not, because the increase in blood flow is equal to the need. We know this because the visual disturbance that some people experience at the start of a migraine is now known to be due to spreading depression, and it is very unusual indeed for any damage to result from a migraine. In fact, some research work suggests that spreading depression might possibly be beneficial in certain rather restricted situations.

So why the concern?
Research over the past 20 years or so, some of it supported by HeadFirst, has shown that if (and only if) the blood supply to the brain is reduced (as happens in a stroke and after some brain injuries and haemorrhages), then spreading depressions start spontaneously in the brain, and now actually themselves make the shortage of blood supply worse - just when blood flow is most needed to recharge the short-circuited nerve cells and astrocytes and to keep them alive.

New results - spreading depression in the injured human brain
For many years after Aristides Leão first described spreading depression, there was real doubt about it might occur in the human brain. Only recently, in a paper in 2002 based on research in patients with head injury in the Intensive Care Unit in King's College Hospital, was it shown beyond doubt spreading depression does indeed happen in humans.

The questions for researchers now:
Not everyone with a brain injury of a particular severity seems to get spreading depression. Why?

When spreading depression happens in the injured brain, how far does it spread?
We have learned to distinguish what types of spreading depression are likely to cause real damage, and drugs are available that can block spreading depression. But before we can use them, we need to test, in patients who actually get spreading depressions after their injury or stroke, whether the drugs actually improve quality of life and speed of recovery.

This means seeing which patients with a brain injury get spreading depression (only about 50 % do so after a serious head injury). At present, in order to detect spreading depression, monitoring electrodes need to be placed on the brain surface. This needs an operation, so the electrodes are only used when the patient already needs neurosurgery as part of their essential treatment.

So, can we detect spreading depression from outside the skull and scalp, for those patients with a serious injury who nevertheless do not need a major operation?

Can we use fairly routine imaging methods (CT and MRI scans) to measure the amount of damage caused by spreading depressions?

So what research would HeadFirst like to fund now?

How to detect spreading depression without needing to place electrodes on the brain surface
Find out what factors make spreading depressions more - or less - frequent. (Some procedures and treatments in routine use in intensive care units may be relevant).
Devise scanning methods to measure the late effects of spreading depressions.
Help more neurosurgeons and intensive care units to contribute to the research - the more research is done, the quicker we shall get the important answers.

International collaboration
King's researchers funded by HeadFirst are leading members of "COSBID" - the Co-operative Study of Brain Injury Depolarisations. Visit its website www.cosbid.org to find out more about the other members, and details of the progress being made.