Mechanisms of interleukin-1 action in neuronal injury

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The blood supply to the brain provides essential oxygen and nutrients to support brain function. During stroke, haemorrhage (bleeding), head injury and certain types of dementia, the blood supply to the brain may be partially reduced or blocked, with fatal consequences for the patient. Our work focuses on understanding what happens in the brain and the rest of the body when the blood supply is reduced, in order to develop safer and more effective treatments for stroke. We have discovered that, in animal brains, a molecule normally associated with inflammation and infection (called interleukin-1 or IL-1 for short) increases when the blood supply is blocked. IL-1 can then kill brain cells, most importantly the nerve cells (neurones), which are essential for the brain to work properly. Our work in animals has already led to the testing of a drug that blocks the effects of IL-1 in stroke patients. However, to develop successful treatments for stroke and other conditions, we need to better understand how IL-1 kills brain cells either directly or by releasing killer molecules from other brain cells. We will test our discoveries in relevant animal models of disease and are well placed to take these findings into patients. This work may lead to new ways of blocking IL-1 and possible new treatments for stroke and related diseases.