RSS Feeds

Email a Friend Printer Friendly

Brain cell research opens way to stroke treatment

April 10, 2000

New ways of limiting the damage caused by strokes, through reducing the energy demands on brain cells, may come about from work being carried out in the Wolfson Institute of Biomedical Research at University College London.

Professor John Garthwaite and colleagues, from the department of neuroscience, are looking at how brain cells talk to each other, what goes wrong to cause brain disorders and how brain cells die under certain conditions.

The hope is that understanding the fundamental mechanisms of the life and death of the brain cell the team can get insights into problems that occur in chronic nuero-degenerative diseases, and in conditions such as stroke.

The researchers are interested in why nitric oxide, ubiquitous in the brain as in many other parts of the body, appears to become toxic in overdose. The mechanism for this involves an amino acid called glutamate. Glutamate - familiar as the flavouring added to Chinese food - is one of the brain's main communicators, but it has been known for some time that too much of it causes cells to die.

In stroke, the blood supply to an area of brain is cut off. The brain is a prolific user of energy, and cutting off blood supply reduces nutrients - glucose - to the brain. To keep glutamate inside the cells, out of harms way, requires energy. Once the energy supply is lost, glutamate comes out. What is more, the process that normally clears away glutamate when it is outside cells become non-functional in such circumstances.

So far it has not proved possible to soak up excess glutamate once it gets outside the cells. There have been attempts to block the proteins that glutamate acts on - but the problem is glutamate is such an important molecule for normal brain function that interfering too much with its actions causes serious side-effects.

The Wolfson researchers are trying other approaches, because in stroke the real problem is lack of energy. The aim therefore is to find ways of reducing the requirement of brain cells for energy.

One particularly important element in this process is the sodium ion. Half the energy of the brain is used getting rid of sodium from cells and pushing it outside.

Explained Professor Garthwaite: "If you can reduce the energy requirement by stopping too much sodium going into cells, you can then stop too much glutamate coming out. We are looking at ways to modulate those channels to preserve brain energy where it is at risk.

"We have found several compounds which give good protection in models of stroke and traumatic injury. What has become clear is that one can tinker with these channels in such a way that preserves their normal functin, but hits abnormal function, which is just what is needed."

Several drugs used to treat epilepsy are based on an ability to inhibit sodium channels, showing this approach can be safe over long periods of time in humans.

Said Professor Garthwaite: "Some epilepsy drugs do have some neuro-protective effects - but we have come across agents which are much more effective than any existing anti-epileptic drugs. We suspect they are able to hit the type of channel which becomes important in causing stroke damage."

The Wolfson researchers are collaborating with the biotech company Vernalis to develop drugs based on the sodium channel blockers.

Added Professor Garthwaite: "The collaboration has been very successful in identifying compounds which have the potential to be medicines to protect the brain in stroke and other conditions.

"For stroke we know enough about the mechanism now to be optimistic. Twenty years ago virtually nothing was known about these conditions. There are reasons for more optimism than has been justifiable at any time in the past. There all sorts of disorders associated with loss of brain cells. One can now start seeing ways of potential treatments.

"It will take longer to understand the root of psychiatric disorders, such as schizophrenia, but in neurological disorders the understanding of what is behind them is bound to, sooner or later, to give rise to, or in some cases give birth to, new or better types of treatments."

ENDS




University College London - UCL