Contribution of Neuro-inflammation to Cerebral Ischaemia

Cerebral ischaemia (CI; stroke, brain injury, vascular dementia, neonatal hypoxia and many other conditions) affects people at all stages of life and is associated with significant mortality and morbidity. Stroke alone causes up to 10% of deaths world-wide and is the leading cause of disability, yet treatment options are extremely limited. A major process contributing to cell death in the ischaemic brain is inflammation. Here we aim to test the hypothesis that inflammasomes are important regulators of brain inflammation and injury.

The project can be defined by the following objectives: 1) To determine the contributions of central and peripheral inflammasomes to ischaemic brain injury, 2) To identify specific inflammasome proteins as therapeutic targets for ischaemic brain injury, and 3) To use nanomedicine to target specific inflammatory processes in the brain.

Methods will include use of molecular and cellular systems to understand regulation of inflammation, in vivo models of ischaemic brain injury, and nanomedicine approaches.

Inflammation in the brain affects the outcome of neurodegenerative disease. For this reason it is an attractive therapeutic target. However, the molecular and cellular mechanisms regulating brain inflammation remain poorly defined. Here we aim to fully elucidate inflammatory regulatory networks in the brain and to establish new therapeutic targets. While this proposal focuses on inflammation after cerebral ischaemia, inflammation is known to contribute to other neurodegenerative diseases such as Alzheimer's and Parkinson's disease and epilepsy, and is now also emerging as a contributor to mental illness such as depression, anxiety and schizophrenia. Thus mechanisms we discover will be of broad relevance to neuro-inflammation and a number of major diseases.