Professor Dame Nancy Rothwell (BSc, PhD, DSc, FMedSci, FRS) - research
Understanding brain disease
Stroke and brain haemorrhage (bleeding into or around the brain) are quite common and devastating disorders. They often result in death for the patient or severe disability, real distress to relatives and carers and the need for major support. The havoc wreaked by these disorders is because part or parts of the brain are starved of vital blood and oxygen (a condition called cerebral ischaemia), so the brain cells die. Our research is trying to understand what causes strokes and what happens in the brain when it is deprived of blood and oxygen, even for short periods of time.
We now know that inflammation is a major culprit in causing damage and death to brain cells when they are deprived of oxygen. We have found that inflammation outside and within the brain can cause stroke and contributes to the damage that follows. We have also discovered that a molecule that causes inflammation in many other tissues seems to be a major cause of brain damage. This molecule, called interleukin-1 (IL-1 for short), is made quickly by our own cells after infection and is made in the brain after a stroke, an injury or other insults. We all have a natural blocker of IL-1 called IL-1 receptor antagonist (shortened to IL-1Ra), which stops IL-1 causing inflammation. A synthetically produced form of this blocker, called Kineret, is used to treat arthritis, and our research suggests that it could be a treatment for stroke and related conditions.
Our current research
We are now undertaking research that spans from molecules and cells through to patient studies. We are trying to understand:
• What makes cells produce IL-1, how it gets out of the cell and how it acts on other cells to cause inflammation and damage.
• How the different cells within the brain interact after damage and how the blood vessels let immune cells into the brain to activate inflammation.
• How infection, obesity and atherosclerosis cause a stroke and stimulate inflammation.
We are also undertaking clinical studies in patients who have had a stroke or sub-arachnoid haemorrhage. He we are:
• Optimising the dose of the IL-1 blocker, Kineret in patients.
• Testing if Kineret could be an effective treatment for stroke and related diseases.
• Identifying the best biomarkers of disease and outcome.
Our research is undertaken at the University of Manchester and at Salford Royal NHS Foundation Trust.