(MRC DTP) Understanding what causes the brain to bleed

Acute cerebrovascular disease remains a major area of unmet clinical need and can present as a range of clinical conditions, from periventricular haemorrhage in preterm babies, through subarachnoid haemorrhage (SAH), ischaemic and haemorrhagic stroke (1). Cerebral cavernous malformations (CCMs) are common vascular malformations occurring within the brain that predispose the affected individual to an increased risk of haemorrhage. It was recently reported that the formation of CCMs in a rodent model was dependent upon TLR4-driven inflammation (2). The NLRP3 inflammasome is a multi-molecular complex that drives inflammation and is an emerging therapeutic target for many major diseases including brain haemorrhage. The NLRP3 inflammasome also requires a TLR4-dependent priming step. In this project we will test the hypothesis that CCM formation and increased haemorrhage risk is NLRP3 dependent. We have developed a unique suite of tools and reagents for interrogating NLRP3 dependent responses and this represents an outstanding opportunity to identify new therapeutic targets and strategies for a disease with a massive unmet clinical need.

https://www.bmh.manchester.ac.uk/research/domains/neuroscience-mental-health/stroke/