Important New Research Identifies How Brain Cells Die During A Stroke

Medical Research Council (MRC) scientists, in collaboration with colleagues from British and Italian universities, have unveiled a mechanism that causes the death of brain cells (neurons) in stroke. The discovery may help explain why some therapy approaches for stroke have been unsuccessful and identifies potential research avenues for the development of new treatments for stroke and other degenerative brain diseases.

Stroke is a consequence of an abrupt interruption of blood flow to the brain. When the blood supply stops, the nerve cells that are directly deprived of oxygen quickly die and release the chemicals that they use to communicate with each other. One of these neurotransmitters – glutamate – spreads to surrounding cells and sets off a process called excitotoxicity, causing much more widespread cell death. Glutamate triggers a flood of calcium ions into the cells and, for reasons not previously understood, the level of calcium continues to rise and this kills the neurons.

The new research, carried out at the MRC’s Toxicology Unit in Leicester, studied the mechanism of calcium overload in neurons after reduction in blood supply to areas of the rat brain. The initial flood of calcium activates enzymes called calpains, which break down the proteins in the cell membrane that normally pump calcium out of the cell.

For many years research has concentrated on trying to block the inflow of calcium, in the hope of preventing brain damage in stroke. But the new findings suggest that the main defect is in the removal of calcium from neurons. This opens up new opportunities for the development of drugs to reduce nerve cell death, not only in stroke but also in degenerative brain disorders.

Each year over 130,000 people suffer from a stroke in England and Wales and acute stroke remains a major cause of death or severe chronic disability.

Research group leader and Unit Director, Professor Pierluigi Nicotera said:
“Work at the MRC Toxicology Unit has unveiled the process that destroys the primary line of defence against calcium accumulation in the brain, which explains the build-up of lethal calcium levels in neurons.

“This is an exciting discovery because these findings go some way to explaining why therapy aimed solely at decreasing calcium entry in brain cells has been unsuccessful. This research identifies potential novel targets for treatment of stroke and other neurodegenerative diseases. The findings may lead to new drugs which will treat these conditions successfully.”

Professor Colin Blakemore, Chief Executive of the Medical Research Council, said:
“This research is an important step forward for the development of new and more effective treatments for stroke – one of the most common conditions affecting the elderly in the UK. And, as the UK’s elderly population continues to grow, so does the importance of targeting the diseases that are common in later life.

“Through the creation of the new UK Clinical Research Collaboration, the MRC will work in partnership with the NHS, medical charities and industry to speed up the development of new treatments so that more patients can benefit more quickly form the latest scientific advances.”